P08.02 Berberine-loaded liposome formulation enhance the phagocytic activity of liposomal imiquimod towards colon cancer cell lines

BackgroundColorectal cancer is the third most commonly diagnosed malignant tumor, taking fourth place in terms of cause of cancer deaths worldwide.1 Unfortunately, the ability of the immune system to distinguish its own from foreign cells is often limited. One of the overexpressed receptors is receptor CD47 - widely distributed glycoprotein on the cell surface of various kind of tumors. It plays a role as ‘don’t eat me’ signal by binding with receptor SIRPα, presents on the cell surface of macrophages.2 Calreticulin, protein occurring on the surface of tumor cells and phagocytes, acts as protein with pro-phagocytic properties. Several natural bioactive substances are predicted to induce immunogenic cell death by translocation calreticulin on the surface of cancer cells which significantly increases the efficiency of their phagocytosis. Moreover, one of the well-known TLR-7 receptor agonists - imiquimod, is involved in phosphorylation of Bruton’s tyrosine kinase leading to the appearance of calreticulin on the surface of macrophages, which increases the efficiency of phagocytosis of tumor cells.3 Combination therapy composed of berberine and imiquimod can be highlighted as effective immunotherapy for colon cancer. However, such an approach remains very limited. Liposomes can serve as promising carriers for targeting delivery and controlled release of anti-cancer agents.Material and MethodsLiposomes were prepared by the thin-film hydration method followed by extrusion. Human colon cancer cell line (LS180 I SW620) and human monocytic cell line (THP-1) were used for experiments. Calreticulin was detected by using confocal microscopy.ResultsThe work presented aimed to develop novel liposomal formulations of berberine and imiquimod which were examined for their efficacy in combination against colorectal cancer cell lines. Liposomal formulations of both compounds were successfully prepared using active loading method with different pH generating agents. All loading methods showed desired characteristics in terms of mean liposome size and polydispersity. The encapsulation efficiency was higher than 95% for almost all used formulations. The in vitro study proved cytotoxicity of berberine loaded liposomal formulations on tested colon cancer cell lines. The results of the immunofluorescence staining indicated that the both compounds triggered calreticulin on the cell surface (colon cancer or macrophages).ConclusionsThe combination of both substances in the liposomal form may generate a synergistic effect on phagocytosis of colon cancer cells.ReferencesArnold M, Sierra MS, Laversanne M, et al. Global patterns and trends in colorectal cancer incidence and mortality. Gut 2017;66:683–691.Sick E, Jeanne A, Schneider C, Dedieu S, Takeda K, Martiny L. CD47 update: a multifaceted actor in the tumor microenvironment of potential therapeutic interest, Br J Pharmacol 2012, 167(7):1415–30.M. Feng, et al., Macrophages eat cancer cells using their own calreticulin as a guide: Roles of TLR and Btk. PNAS 2015;112( 7):2145–2150.Disclosure InformationM. Mianowska: B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); Significant; National Science Center, Poland. M. Zaremba-Czogalla: None. A. Zygmunt: None. J. Gubernator: None.

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Anticancer effects of bifidobacteria on colon cancer cell lines

Cancer Cell International ◽

10.1186/s12935-021-01971-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zeinab Faghfoori ◽

Mohammad Hasan Faghfoori ◽

Amir Saber ◽

Azimeh Izadi ◽

Ahmad Yari Khosroushahi

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Colon Cancer Cell ◽

Rt Pcr ◽

Anticancer Effects ◽

Colon Cancer Cell Lines ◽

Apoptotic Genes

Abstract Background Colorectal cancer (CRC), with a growing incidence trend worldwide, is resistant to apoptosis and has uncontrolled proliferation. It is recently reported that probiotic microorganisms exert anticancer effects. The genus Bifidobacterium, one of the dominant bacterial populations in the gastrointestinal tract, has received increasing attention because of widespread interest in using it as health-promoting microorganisms. Therefore, the present study aimed to assess the apoptotic effects of some bifidobacteria species on colon cancer cell lines. Methods The cytotoxicity evaluations performed using MTT assay and FACS-flow cytometry tests. Also, the effects of five species of bifidobacteria secretion metabolites on the expression level of anti- or pro-apoptotic genes including BAD, Bcl-2, Caspase-3, Caspase-8, Caspase-9, and Fas-R studied by real-time polymerase chain reaction (RT-PCR) method. Results The cell-free supernatant of all studied bifidobacteria significantly decreased the survival rates of colon cancer cells compared with control groups. Flow cytometric and RT-PCR results indicated that apoptosis is induced by bifidobacteria secretion metabolites and the mechanism for the action of bifidobacteria species in CRC prevention could be down-regulation and up-regulation of anti-apoptotic and, pro-apoptotic genes. Conclusions In the present study, different bifidobacteria species showed anticancer activity on colorectal cancer cells through down-regulation and up-regulation of anti-apoptotic and pro-apoptotic genes. However, further studies are required to clarify the exact mechanism of apoptosis induction by bifidobacteria species.

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Incomplete processing of progastrin expressed by human colon cancer cells: role of noncarboxyamidated gastrins

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1994.266.3.g459 ◽

1994 ◽

Vol 266 (3) ◽

pp. G459-G468 ◽

Cited By ~ 6

Author(s):

P. Singh ◽

Z. Xu ◽

B. Dai ◽

S. Rajaraman ◽

N. Rubin ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Human Colon ◽

Cancer Cell Lines ◽

Colon Cancer Cell ◽

Colon Cancer Cells ◽

Human Colon Cancer ◽

Colon Cancer Cell Lines

Gastrin is mitogenic for several colon cancers. To assess a possible autocrine role of gastrin in colon cancers, we examined human colon cancer cell lines for expression of gastrin mRNA and various forms of gastrin. Gastrin mRNA was not detected in the majority of colon cancer cell lines by Northern hybridization but was detected in all human colon cancer lines by the sensitive method of reverse transcriptase-polymerase chain reaction (PCR). Gastrin mRNA was quantitated by the competitive PCR method. The majority of cell lines expressed very low levels of gastrin mRNA (< 1-5 copies/cell); only one cell line expressed > 20 copies/cell. The mature carboxyamidated form of gastrin was not detected in any of the cell lines by radioimmunoassay or immunocytochemistry. Results suggested that either gastrin mRNA expressed by colon cancer cells was altered (mutated) or posttranslational processing of progastrin was incomplete. Gastrin cDNA from all the colon cancer cell lines had an identical sequence to the published sequence of human gastrin cDNA. Specific antibodies against precursor forms of gastrin were used, and significant concentrations of nonamidated (glycine-extended) and prepro forms of gastrin were measured in tumor extracts of representative colon cancer cell lines. The presence of precursor forms of gastrin suggested a lack of one or more of the processing enzymes and/or cofactors. Significant concentrations of the processing enzyme (peptidylglycine alpha-amidating monooxygenase) were detected in colon cancer cells by immunocytochemistry. Therefore, lack of other cofactors or enzymes may be contributing to incomplete processing of precursor forms of gastrin, which merits further investigation. Since low levels of gastrin mRNA were expressed by the majority of human colon cancer cell lines and progastrin was incompletely processed, it seems unlikely that gastrin can function as a viable autocrine growth factor for colon cancer cells. High concentrations of glycine-extended gastrin-17 (GG) (> 10(-6) M) were mitogenic for a gastrin-responsive human colon cancer (DLD-1) cell line in vitro. It remains to be seen if GG or other precursor forms of gastrin are similarly mitogenic in vivo, which may then lend credibility to a possible autocrine role of gastrinlike peptides in colon cancers.

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Dual Targeting of the Epidermal Growth Factor Receptor Using the Combination of Cetuximab and Erlotinib: Preclinical Evaluation and Results of the Phase II DUX Study in Chemotherapy-Refractory, Advanced Colorectal Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2011.38.6599 ◽

2012 ◽

Vol 30 (13) ◽

pp. 1505-1512 ◽

Cited By ~ 71

Author(s):

Andrew J. Weickhardt ◽

Tim J. Price ◽

Geoff Chong ◽

Val Gebski ◽

Nick Pavlakis ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Epidermal Growth Factor Receptor ◽

Cell Lines ◽

Cancer Cell ◽

Growth Factor Receptor ◽

Cancer Cell Lines ◽

Colon Cancer Cell ◽

Colon Cancer Cell Lines ◽

Epidermal Growth

Purpose This preclinical and phase II study evaluated the efficacy and safety of the combination of cetuximab and erlotinib in metastatic colorectal cancer (mCRC). Patients and Methods The activity and mechanism of action of the combination of cetuximab plus erlotinib were investigated in vitro in colorectal cancer cell lines. In the clinical study, patients with chemotherapy-refractory mCRC were treated with cetuximab 400 mg/m2 as a loading dose and then weekly cetuximab 250 mg/m2 with erlotinib 100 mg orally daily. The primary end point was response rate (RR), which was evaluated separately in KRAS wild-type (WT) versus KRAS mutant tumors. Secondary end points included toxicity, progression-free survival (PFS), and overall survival. Target accrual was 50 patients, with a one-stage design. Results Preclinical studies demonstrated synergistic activity of cetuximab and erlotinib cotreatment on growth inhibition of colon cancer cell lines both as a result of enhanced inhibition of the epidermal growth factor receptor pathway and differential effects on STAT3. In the clinical study, 50 patients were enrolled, with 48 patients evaluable for response. The overall RR was 31% (95% CI, 26% to 57%), with a median PFS of 4.6 months (95% CI, 2.8 to 5.6 months). RR was 41% (95% CI, 26% to 57%) in KRAS WT tumors, with a median PFS of 5.6 months (95% CI, 2.9 to 5.6 months). There was no response in 11 patients with KRAS mutations. Frequent grade 3 and 4 toxicities were rash (48%), hypomagnesaemia (18%), and fatigue (10%). Conclusion The combination of cetuximab and erlotinib synergistically inhibits growth of colon cancer cell lines, achieves promising efficacy in patients with KRAS WT mCRC, and merits evaluation in further randomized studies.

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MicroRNA silencing of CNN1 and CNN2 protein family members regulates biology processes in colorectal cancer by targeting the p53 signal pathway

10.21203/rs.3.rs-38064/v1 ◽

2020 ◽

Author(s):

Fuda Huang ◽

Mingwei Wei ◽

Anmin Wang ◽

Ya Zhang ◽

Zebang Qin ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Cycle ◽

Colon Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Colon Cancer Cell ◽

Expression Levels ◽

Colon Cancer Cell Lines ◽

Cancer Tissues

Abstract BackgroundCalponin was first defined as a striated muscle troponin T-like protein that binds actin thin filaments to regulate smooth muscle contraction. There are few studies of CNN1 and CNN2 in colorectal cancer, and the roles these two genes play in colorectal cancer cell lines and the mechanisms by which they act are unknown.MethodsWe used immunohistochemistry to identify expression of the two genes in the cancer tissues. RT-PCR was used to measure expression levels of microRNA. W performed western blots to measure changes in signaling pathways in the context of expression interference.Meanwhile, the same method was used to measure binding relationship between the two genes and key pathway proteins. To determine the relationship between microRNA and gene mRNA, we used the reporter gene method. We used the chi-square and t-test methods to analyze the significance and correlations of the data.Results and conclusionsExpression levels of CNN1 were lower in colon cancer tissues than in normal mucosal tissues. After downregulating CNN1, the cell cycle in colon cancer cell lines progressed quickly, and the expression of related pathway proteins also increased. Expression levels of CNN2 were higher in colon cancer tissues, and its downregulation significantly inhibited cell cycle progression in colon cancer cell lines. We confirmed correlations between the expression of microRNA and CNN2 using data analysis.Bars indicate ± standard errors.*p < 0.05; **p < 0.01 compared with the control. The inhibition of the expression of CNN2 mRNA using microRNA was confirmed using western blot. The combination of the two at the mechanism level was also demonstrated using the reporter gene method.

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Anticancer effects of Bifidobacteria on colon cancer cell lines

10.21203/rs.3.rs-120251/v2 ◽

2021 ◽

Author(s):

Zeinab Faghfoori ◽

Mohammad Hasan Faghfoori ◽

Amir Saber ◽

Azimeh Izadi ◽

Ahmad Yari Khosroushahi

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Colon Cancer Cell ◽

Rt Pcr ◽

Anticancer Effects ◽

Colon Cancer Cell Lines ◽

Apoptotic Genes

Abstract Background: Colorectal cancer (CRC), with a growing incidence trend worldwide, is resistant to apoptosis and have the uncontrolled proliferation. It is recently reported that probiotic microorganisms exert anticancer effects. The genus Bifidobacterium, one of the dominant bacterial populations in the gastrointestinal tract, has received increasing attention because of widespread interest in using as health-promoting microorganisms. Therefore, the present study aimed to assess the apoptotic effects of some bifidobacteria species on colon cancer cell lines.Methods: The cytotoxicity evaluations performed using MTT assay and FACS-flow cytometry tests. Also, the effects of five species of bifidobacteria secretion metabolites on the expression level of anti- or pro-apoptotic genes including BAD, Bcl-2, Caspase-3, Caspase-8, Caspase-9, and Fas-R studied by real-time polymerase chain reaction (RT-PCR) method. Results: The cell-free supernatant of all studied bifidobacteria significantly decreased the survival rates of colon cancer cells compared with control groups. Flow cytometric and RT-PCR results indicated that apoptosis is induced by bifidobacteria secretion metabolites and the mechanism for the action of bifidobacteria species in CRC prevention could be down-regulation and up-regulation of anti-apoptotic and, pro-apoptotic genes.Conclusions: In the present study, different bifidobacteria species showed anticancer activity on colorectal cancer cells through down-regulation and up-regulation of anti-apoptotic and pro-apoptotic genes. However, further studies are required to clarify the exact mechanism of apoptosis induction by bifidobacteria species.

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725 Immunomodulation by targeting PDL-1 in colon cancer using nuclear receptor 4A1 (NR4A1) antagonists

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-sitc2021.725 ◽

2021 ◽

Vol 9 (Suppl 3) ◽

pp. A754-A755

Author(s):

Maen Abdelrahim ◽

Kumaravel Mohankumar ◽

Keshav Karki ◽

Stephen Safe

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Colon Cancer Cell ◽

Colon Cancer Cells ◽

Western Blots ◽

Colon Cancer Cell Lines

BackgroundThe nuclear orphan receptor 4A1 (NR4A1, Nur77, TR3) is overexpressed in multiple solid tumors including colorectal tumors and is a negative prognostic factor for patient survival.1–3 NR4A1 is expressed in colon cancer cells and exhibit pro-oncogenic activity4 and results of examination of several colon cancer cell lines show that PD-L1 expression is limited and NR4A1 and PD-L1 are co-expressed in SW480 and RKO colon cancer cell lines. Previous studies showed that PD-L1 was regulated by NR4A1 which activates transcription factor Sp1 bound to the PD-L1 gene promoter.5–7 Knockdown of NR4A1 or Sp1 by RNA interference or treatment with mithramycin an inhibitor of Sp-mediated transcription decreased expression of PD-L1 in RKO and SW480 colon cancer cell lines.MethodsSW480, RKO and MC-38 cells were used in this study. Cells were treated for 24 hrs with DIM series of compounds.ResultsCurrent data coupled with ongoing gene expression and PD-L1 promoter studies demonstrate that PD-L1 expression is regulated by NR4A1/Sp1 in colon cancer cells (figures 1–3). Bis-indole derived NR4A1 ligand that act as receptor antagonists have been developed in this laboratory and these compounds block pro-oncogenic NR4A1-regulated genes/pathways. Treatment of RKO and SW480 colon cancer cell lines with a series of potent 1,1-bis(3′-indolyl)-1-(3,5-disubstitutedphenyl) analogs decreased expression of PD-L1. These results show that bis-indole derived NR4A1 antagonists act as small molecule mimics of immunotherapeutics that target PD-L1. In vivo applications of NR4A1 ligands that target PD-L1 and their effects on tumor growth and immune surveillance are currently being investigated.ConclusionsBis-indole derived NR4A1 antagonists inhibit PD-L1 expression. NR4A1/SP1 regulates PD-L1 and is inhibited by NR4A1 antagonist. NR4A1 ligands such as DIM-3-Br-5-OCF3 were among the most potent of the substituted DIM compounds and ongoing in vivo studies show that this DIM compound also inhibits tumor growth in a syngenic mouse model (data not shown). Data from this study demonstrate the pro-oncogenic activity of NR4A1 and show that the synthetic buttressed analog DIM-3-Br-5-OCF3 acts as an NR4A1 antagonist and inhibits PD-L1 expression. These drugs can be developed for future clinical applications.Referenceswww.cancer.org/cancer/colon-rectal-cancer/about/key-statistics.html.Garcia-Villatoro et al., Effects of high-fat diet and intestinal aryl hydrocarbon receptor deletion on colon carcinogenesis. Am J Physiol Gastrointest Liver Physiol 2020;318(3):G451–G463.Safe S, Jin UH, Hedrick E, et al. Minireview: role of orphan nuclear receptors in cancer and potential as drug targets. Mol Endocrinol 2014;28(2):157–72.Maxwell MA, Muscat GE. The NR4A subgroup: immediate early response genes with pleiotropic physiological roles. Nucl Recept Signal 2006;4:e002.Lee SO, Li X, Hedrick E, et al. Diindolylmethane analogs bind NR4A1 and are NR4A1 antagonists in colon cancer cells. Mol Endocrinol 2014;28(10):1729–39.Safe S, Kim K. Non-classical genomic estrogen receptor (ER)/specificity protein and ER/activating protein-1 signaling pathways. J Mol Endocrinol 2008;41(5):263–75.Tao LH, Zhou XR, Li FC, Chen Q, Meng FY, Mao Y, et al. A polymorphism in the promoter region of PD-L1 serves as a binding-site for SP1 and is associated with PD-L1 overexpression and increased occurrence of gastric cancer. Cancer Immunol Immunother 2017;66(3):309–18.Abstract 725 Figure 1NR4A1 inactivation inhibits PD-L1 expression. SW480, RKO and MC-38 cells were transfected with siCtrl (non-specific oligonucleotide) and two oligonucleotides targeting NR4A1 (siNR4A1(1) and siNR4A1(2)) or PD-L1 (siPD-L1(1) and siPD-L1(2)) for 72 hrss. Protein expression from whole cell lysates were analyzed by western blots and effects on PD-L1 expression were determinedAbstract 725 Figure 2Sp1 inactivation inhibits PD-L1 expression. SW480, RKO and MC-38 cells were transfected with siCtrl and oligonucleotides targeting Sp1 (siSp1(1) and siSp1(2)) for 72 hrs as well as treated with Mithrsamycin (150 and 300 nM) for 24 hrs. Protein expression from was analyzed by western blots and effects on PD-L1 levels were determined.Abstract 725 Figure 3Role of NR4A1/Sp in regulation of PD-L1. SW480, RKO and MC-38 cells were treated with DIM-3-Br-5-OCF3 for 24 hrss and protein interactions with the GC-rich PD-L1 promoter region were analyzed by ChIP using primers encompassing GC-rich region of the promoter

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Expression of AEG-1 mRNA and protein in colorectal cancer patients and colon cancer cell lines

Journal of Translational Medicine ◽

10.1186/1479-5876-10-109 ◽

2012 ◽

Vol 10 (1) ◽

pp. 109 ◽

Cited By ~ 44

Author(s):

Sebastian Gnosa ◽

Yang-Mei Shen ◽

Chao-Jie Wang ◽

Hong Zhang ◽

Johannes Stratmann ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Cancer Patients ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Colon Cancer Cell ◽

Colon Cancer Cell Lines ◽

Colorectal Cancer Patients

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SLC7A5 Promotes Colorectal Cancer Progression by Regulating Cell Cycle and Migration

10.21203/rs.3.rs-192581/v1 ◽

2021 ◽

Author(s):

Baiyou Tang ◽

Lihua Zhang ◽

Jing Yu ◽

Mingjing Peng ◽

Yu Cheng ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Cycle ◽

Colon Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Colon Cancer Cell ◽

Functional Enrichment ◽

Public Database ◽

Colon Cancer Cell Lines

Abstract Background: Solute carrier family 7 member 5 (SLC7A5) was identified highly expressed and as a key participant in various tumor development; however, the role it played in colorectal cancer remains unclear. Methods and Results: In the current study, the expression of SLC7A5 were systematically mined in public databases and validated by real-time PCR in colon cancer and normal tissues. And then, the co-expression and pathway analysis got from public database, which indicated the potential influence of SLC7A5 for the etiology of colorectal cancer, were evaluated in the colon cancer cell lines by loss of SLC7A5 function experiment, flow cytometry, western blot, and wound healing assay. The results showed that the mRNA expression of SLC7A5 was significantly higher in colorectal cancer tissues than that in the non-tumor controls for GEO and TCGA datasets as well as 40 pairs of Xiangya clinical samples. The functional enrichment analysis based on public database showed that the pathways enriched most were cell cycle and epithelial-to-mesenchymal transition (EMT), and Cyclin D1 (CCND1) were the only gene that had a significant positive correlation with SLC7A5. Loss of SLC7A5 function in colon cancer cell lines could arrest cell cycle at G1 phase by down-regulating CCND1 and CDK2 protein expression, and may reduce cell migration by reversing EMT though upregulation of E-Cadherin and downregulation of zonula occludens-1. Conclusion: SLC7A5 is likely associated with the progression of colon cancer.

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Cysteine-Rich Intestinal Protein 1 Silencing Inhibits Migration and Invasion in Human Colorectal Cancer

Cellular Physiology and Biochemistry ◽

10.1159/000485357 ◽

2017 ◽

Vol 44 (3) ◽

pp. 897-906 ◽

Cited By ~ 3

Author(s):

Guoyang He ◽

Liyuan Zou ◽

Lin Zhou ◽

Peiqiong Gao ◽

Xinlai Qian ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Cell Proliferation ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Colon Cancer Cell ◽

Migration And Invasion ◽

Tissue Samples ◽

Colon Cancer Cell Lines

Background/Aims: Cysteine-rich intestinal protein 1 (CRIP1), a member of the LIM/double zinc finger protein family, is abnormally expressed in several tumour types. However, few data are available on the role of CRIP1 in cancer. In the present study, we aimed to investigate the expression profile and functions of CRIP1 in colorectal cancer. Methods: To examine the protein expression level of CRIP1, immunohistochemistry (IHC) was performed on 56 pairs of colon cancer tissue samples. Western blotting was performed to investigate CRIP1 protein expression in four colon cancer cell lines. The endogenous expression of CRIP1 was suppressed using short interfering RNAs (siRNAs). Cell proliferation assays were used to determine whether CRIP1 silencing affected cell proliferation. Flow cytometry analysis was used to detect cell apoptosis. The effects of silencing CRIP1 on cell migration and invasion was detected using the transwell and wound-healing assays. Results: IHC analysis showed that protein level of CRIP1 was significantly higher in tumour tissue samples than in paired non-tumour tissue samples and that the CRIP1 level was higher in metastatic tissue samples than in non-metastatic tissue samples. In addition, protein levels of CRIP1 were higher in highly metastatic colon cancer cell lines than in colon cancer cell lines with low metastasis. Further, CRIP1 silencing had no effect on cell proliferation or apoptosis in SW620 and HT29 cells. CRIP1 silencing suppressed cell migration and invasion obviously in SW620 and HT29 cells. Conclusion: The present study provides new evidence that abnormal expression of CRIP1 might be related to the degree of metastasis in colorectal cancer and that CRIP1 silencing could effectively inhibit migration and invasion during colorectal cancer development. These findings might aid the development of a biomarker for colon cancer prognosis and metastasis, and thus help to treat this common type of cancer.

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Clinicopathological and prognostic significance of TM4SF5 in colorectal cancer

10.21203/rs.3.rs-153931/v1 ◽

2021 ◽

Author(s):

Zhongbei Yu ◽

Jun Feng ◽

Yulan Zhu ◽

Xiaolu Xie ◽

Hao Huang ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Prognostic Value ◽

Cancer Cell Lines ◽

Colon Cancer Cell ◽

Biological Behavior ◽

Migration And Invasion ◽

Colon Cancer Cell Lines

Abstract Background Transmembrane 4 L six family member 5 (TM4SF5) has been found to play a vital role in the cancer process, but the relationship between TM4SF5 and colorectal cancer remains unclear. Therefore, the present study aimed to investigate the clinical and prognostic value of TM4SF5 in colorectal cancer (CRC). Methods Immunohistochemistry and RT-qPCR were used to identify the clinical significance and prognostic value of TM4SF5 expression in colon cancer. The expression of TM4SF5 was knocked down using the siRNA method to evaluate the role of TM4SF5 in regulating the biological behavior of colon cancer cell lines. Results The immunohistochemistry study revealed that the expression of TM4SF5 in human colorectal cancer tissues was significantly higher than that in adjacent normal tissues (P < 0.0001). However, there was no correlation between the expression of TM4SF5 and the clinicopathological features of these patients. The RT-qPCR analysis revealed that the mRNA expression of TM4SF5 was higherin colon cancer cell lines than in normal cells (P < 0.05). The survival analysis revealed that the overall survival (OS) rate of patients with a low expression of TM4SF5 was significantly higher, when compared to patients with a high expression of TM4SF5 (P = 0.048). The COX model revealed that the expression of TM4SF5 (P < 0.001) and clinical stage (P = 0.025) can be used as independent prognostic factors for patients with colon cancer. In addition, the knockdown of TM4SF5 in colon cancer cell lines LoVo, SW480, RKO and HCT-116 significantly reduced the ability of cells (such as proliferation, migration and invasion). Conclusion The present results indicate that the increase in TM4SF5 expression in human colon cancer is associated with cancer progression and poor survival, and that its intervention can be an important therapeutic strategy against colon cancer.

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