scholarly journals Qingjie Fuzheng Granule Inhibited the Migration and Invasion of Colorectal Cancer Cells by Regulating the lncRNA ANRIL/let-7a/TGF-β1/Smad Axis

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Ling Zhang ◽  
Jianxin Liu ◽  
Shan Lin ◽  
Jingzhuang Tan ◽  
Bin Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Wound Healing ◽  
Mucosal Damage ◽  
Migration And Invasion ◽  
Colorectal Cancer Cells ◽  
Smad Signaling Pathway ◽  
Mtt Assays ◽  
Tgf Β1 ◽  
Hct116 Cells

Qingjie Fuzheng granule (QFG) promotes cancer cell apoptosis and ameliorates intestinal mucosal damage caused by 5-fluorouracil. However, the antitumor role of QFG in colorectal cancer (CRC) progression remains unclear. In this study, the growth of HCT-8 and HCT116 cells incubated with various concentrations of QFG for 24 and 48 h was evaluated using MTT assays; their abilities of migration and invasion were investigated through wound healing and Transwell assays. The expression of lncRNA ANRIL, let-7a, and the TGF-β1/Smad signaling pathway components was assessed using real-time PCR and western blotting. The results elicited that QFG significantly suppressed the growth of HCT-8 and HCT116 cells; the half-maximal inhibitory concentrations (IC50) of QFG for HCT-8 and HCT116 cells for 48 h were 1.849 and 1.608 mg/mL, respectively. The abilities of wound healing, migration, and invasion of HCT-8 and HCT116 cells were dose-dependently decreased by QFG treatment for 24 h, respectively. QFG decreased the expression of lncRNA ANRIL, TGF-β1, phosphorylated (p)-Smad2/3, Smad4, and N-cadherin and upregulated the expression of let-7a in HCT-8 and HCT116 cells. Collectively, our data demonstrated that QFG inhibited the metastasis of CRC cells by regulating the lncRNA ANRIL/let-7a/TGF-β1/Smad axis, indicating that they might serve as an adjunctive medicine for CRC treatment.

scholarly journals Cooperation of SRPK2, Numb and p53 in the malignant biology and chemosensitivity of colorectal cancer

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Guosen Wang ◽  
Weiwei Sheng ◽  
Jingtong Tang ◽  
Xin Li ◽  
Jianping Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Chemical Agent ◽  
Cell Migration And Invasion ◽  
Agent Treatment ◽  
Hct116 Cells

Abstract Serine-arginine protein kinase 2 (SRPK2) is aberrantly expressed in human malignancies including colorectal cancer (CRC). However, little is known about the molecular mechanisms, and the role of SRPK2 in chemosensitivity remains unexplored in CRC. We recently showed that SRPK2 promotes pancreatic cancer progression by down-regulating Numb and p53. Therefore, we investigated the cooperation between SRPK2, Numb and p53 in the cell migration, invasion and chemosensitivity of CRC in vitro. Here, we showed that SRPK2 expression was higher in CRC tumors than in nontumor tissues. SRPK2 expression was positively associated with clinicopathological characteristics of CRC patients, including tumor differentiation, T stage, N stage and UICC stage. Additionally, SRPK2 had no association with mutant p53 (mtp53) in SW480 and SW620 cells, but negatively regulated Numb and wild-type p53 (wtp53) in response to 5-fluorouracil or cisplatin treatment in HCT116 cells. Moreover, SRPK2, Numb and p53 coimmunoprecipitated into a triple complex with or without the treatment of 5-fluorouracil in HCT116 cells, and p53 knockdown reversed the up-regulation of wtp53 induced by SRPK2 silencing with chemical agent treatment. Furthermore, overexpression of SRPK2 increased cell migration and invasion and decreased chemosensitivity to 5-fluorouracil or cisplatin in HCT116 cells. Conversely, SRPK2 silencing decreased cell migration and invasion and increased chemosensitivity to 5-fluorouracil or cisplatin, yet these effects could be reversed by p53 knockdown under chemical agent treatment. These results thus reveal a novel role of SRPK2-Numb-p53 signaling in the progression of CRC and demonstrate that SRPK2 is a potential therapeutic target for CRC clinical therapy.

scholarly journals Casein Kinase-1-Alpha Inhibitor (D4476) Sensitizes Microsatellite Instable Colorectal Cancer Cells to 5-Fluorouracil via Authophagy Flux Inhibition

2021 ◽  
Vol 69 (1) ◽  
Author(s):  
Morvarid Siri ◽  
Hamid Behrouj ◽  
Sanaz Dastghaib ◽  
Mozhdeh Zamani ◽  
Wirginia Likus ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Chemotherapy Resistance ◽  
Casein Kinase ◽  
Autophagy Flux ◽  
Casein Kinase 1 ◽  
Colorectal Cancer Cells ◽  
High Level ◽  
Casein Kinase 1 Alpha ◽  
Hct116 Cells

AbstractAdjuvant chemotherapy with 5-fluorouracil (5-FU) does not improve survival of patients suffering from a form of colorectal cancer (CRC) characterized by high level of microsatellite instability (MSI-H). Given the importance of autophagy and multi-drug-resistant (MDR) proteins in chemotherapy resistance, as well as the role of casein kinase 1-alpha (CK1α) in the regulation of autophagy, we tested the combined effect of 5-FU and CK1α inhibitor (D4476) on HCT116 cells as a model of MSI-H colorectal cancer. To achieve this goal, the gene expression of Beclin1 and MDR genes, ABCG2 and ABCC3 were analyzed using quantitative real-time polymerase chain reaction. We used immunoblotting to measure autophagy flux (LC3, p62) and flow cytometry to detect apoptosis. Our findings showed that combination treatment with 5-FU and D4476 inhibited autophagy flux. Moreover, 5-FU and D4476 combination therapy induced G2, S and G1 phase arrests and it depleted mRNA of both cell proliferation-related genes and MDR-related genes (ABCG2, cyclin D1 and c-myc). Hence, our data indicates that targeting of CK1α may increase the sensitivity of HCT116 cells to 5-FU. To our knowledge, this is the first description of sensitization of CRC cells to 5-FU chemotherapy by CK1α inhibitor. Graphic abstract

scholarly journals Circ_0026344 overexpression inhibits the migration, invasion, and enhances apoptosis of colorectal cancer cells by sponging miR-31

2020 ◽  
Author(s):  
Ye Jin ◽  
Lingli Yu ◽  
Bin Zhang ◽  
Yun Chen ◽  
Changfeng Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Flow Cytometry ◽  
Wound Healing ◽  
Cell Lines ◽  
Opposite Effect ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Colorectal Cancer Cells ◽  
Reporter Assays ◽  
E Cadherin

Abstract Background: Circ_0026344 was reported to be associated with the metastasis of colorectal cancer (CRC). This study aimed to investigate the expression of circ_0026344 in CRC and the effect mechanisms of circ_0026344 on CRC.Methods: The expressions of circ_0026344 and miR-31 in clinical CRC tissues or CRC cell lines were analyzed by qPCR. The target of circ_0026344 was predicted and verified by CircInteractome and dual-luciferase reporter assays. The correlation between circ_0026344 and miR-31 expression was analyzed using Pearson analysis. After the CRC cells were overexpressed circ_0026344 or miR-31 or silenced circ_0026344, the viability, apoptosis, migration, and invasion of CRC cells were evaluated by CCK-8, flow cytometry, wound healing, and transwell. Also, the expressions of miR-31, Bcl-2, Bax, E-cadherin, and N-cadherin in the cells were detected by qPCR or Western blot. Results: Circ_0026344 was low-expressed in CRC tissues and cell lines. Circ_0026344 sponged miR-31 which was high-expressed in CRC tissues. The expression of circ_0026344 was negatively correlated to the expression of miR-31. The miR-31 expression could be down-regulated by circ_0026344 overexpression. Circ_0026344 overexpression inhibited the cell viability, migration, and invasion; and enhanced the apoptosis of CRC cells. Circ_0026344 overexpression decreased the expressions of Bcl-2 and N-cadherin and increased the expressions of Bax and E-cadherin in CRC cells. Circ_0026344 silencing and miR-31 overexpression had an opposite effect on CRC cells as circ_0026344 overexpression. Furthermore, miR-31 overexpression counteracted the effect of circ_0026344 overexpression.Conclusion: Circ_0026344 overexpression inhibited the migration, invasion, and enhanced apoptosis of CRC cells by sponging miR-31.

Effect of neuropilin-2 expression on TGF-β1-epithelial-mesenchymal transition in colorectal cancer cells.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 414-414
Author(s):  
C. Grandclement ◽  
R. Bedel ◽  
B. Kantelip ◽  
E. Viel ◽  
J. Remy Martin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Human Colon ◽  
Mesenchymal Transition ◽  
Colorectal Cancer Cells ◽  
Tgf Β1

414 Background: Initially characterized as neuronal receptors, Neuropilins (NRPs) were also found to be expressed in endothelial cells and subsequently were shown to play a role in the development of the vascular system. NRP family consists of two genes, neuropilin-1 (NRP1) and neuropilin-2 (NRP2).The multiple functions of NRPs were recently highlighted by the identification of NRP role in oncogenesis. In this study, we first confirmed the role of NRP2 in tumor progression. We also extended the understanding of NRP2 oncogenic functions by investigating the ability of NRP2 to orchestrate epithelial-mesenchymal transition (EMT) in colorectal cancer cells. Methods: We have generated human colon cancer cell lines transfected with NRP2 transgene or siRNA to investigate NRP2 involvement in EMT. First, the oncogenic functions of NRP2 were studied in vitro by MTT, soft agar, invasion assays and in vivo using xenografts experiments. Ability of NRP2 to orchestrate EMT was then investigated by flow cytometry, immunohistochemical (IHC) staining, western-blotting and quantitative real-time PCR. Results: IHC staining revealed that NRP2 is expressed in human colon and breast carcinomas while it is not expressed in healthy tissues. Then, we confirmed that NRP2 increases tumor proliferation, colony formation, invasion and xenograft formation. Moreover, NRP2-expressing cells displayed an immunohistochemical phenotype of EMT characterized by the loss of E-Cadherin and an increase of vimentin. Furthermore, NRP2 expression promotes transforming-growth factor-β1 (TGF- β1) signaling, leading to an increased phosphorylation of the Smad2/3 complex in colorectal cancer cell lines. Specific inhibition of NRP2 using siRNA or treatment with specific TGFβRI kinase inhibitors prevented this phosphorylation and the EMT, suggesting that NRP2 cooperates with TGFRI to promote EMT in colorectal carcinoma. Conclusions: Our findings have reinforced the essential role of NRP2 in cancer progression and demonstrated that NRP2 expression confers to tumor cell lines the hallmarks of EMT. Moreover, in the current work, we present evidence for the therapeutic value of NRP2 targeting. No significant financial relationships to disclose.

LncRNA Phosphoglucomutase 5-Antisense RNA 1 Modulation Affects the Proliferation and Metastasis Capabilities via Upregulating miR-484 Expression in Colorectal Cancer Cells

2021 ◽  
Vol 11 (1) ◽  
pp. 176-184
Author(s):  
Yongsheng Zhou ◽  
Jijin Wu ◽  
Shushan Yin
Keyword(s):  
Colorectal Cancer ◽  
Cell Viability ◽  
Antisense Rna ◽  
Cell Counting ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Down Regulation ◽  
Colorectal Cancer Cells ◽  
Proliferation And Metastasis ◽  
Hct116 Cells

Background: LncRNA emerges to be helpful in the diagnosis and treatment of colorectal cancer (CRC). We intended to uncover the underlying modulatory pathway of lncRNA PGM5-AS1 in CRC cells. Materials and Methods: The prediction of target of PGM5-AS1 was by informatics and verified by dual luciferase assay. Transcription levels of PGM5-AS1 and miR-484 were determined by qPCR. Cell viability was measured by cell counting kit (CCK)-8. Migration rate was assessed by wound healing assay and invasion by Transwell. Cell growth was evaluated by colony formation assay. Results: PGM5-AS1 was up-regulated in CRC tissue and cell lines while its down-regulation contributed to the decreasing of cell viability, growth, migration and invasion capabilities of SW480 and HCT116 cells. Moreover, miR-484 was the target of PGM5-AS1. In addition, the down-regulation of PGM5-AS1 partially restored the elevated cell viability, growth, migration and invasion capacities following the inhibition of miR-484 expression in SW480 and HCT116 cells. Conclusions: The loss of miR-484 expression in CRC might be involved in the promotion and metastasis of CRC, the consequence which could be the result of the overexpression of PGM5-AS1. Hence, the down-regulation of PGM5-AS1 could be a therapeutic target in the prevention or intervention of CRC.

scholarly journals LPS Upregulated VEGFR-3 Expression Promote Migration and Invasion in Colorectal Cancer via a Mechanism of Increased NF-κB Binding to the Promoter of VEGFR-3

2016 ◽  
Vol 39 (5) ◽  
pp. 1665-1678 ◽  
Author(s):  
Guangwei Zhu ◽  
Qiang Huang ◽  
Wei Zheng ◽  
Yongjian Huang ◽  
Jin Hua ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Neutralizing Antibody ◽  
High Expression ◽  
Migration And Invasion ◽  
Colorectal Cancer Cells ◽  
Cancer Tissues ◽  
The Relationship

Background and Aim: Lipopolysaccharide(LPS) could promote the progression of colorectal cancer, but the specific regulatory mechanisms are largely unknown. So, this study aim to clarify the mechanisms that LPS upregulated VEGFR-3, which promotes colorectal cancer cells migration and invasion with a mechanism of increased NF-κB bind to the promoter of VEGFR-3. Methods: The present study examined the VEGFR-3 expression in colorectal cancer tissues and analyzed the relationship between the VEGFR-3 expression with clinical parameters. PCR, Western blot, CCK-8, colone formation assay, and Transwell assay detected that LPS promoted the migration and invasion and the role of VEGFR-3 in the process of colorectal carcinoma in vitro. Used the methods of promoter analysis, EMSA assay and ChIP assay to explore the mechanisms LPS increased the expression of VEGFR-3. Results: VEGFR-3 was significantly high expression in the colorectal cancer tissues. And the high expression was associated with the TNM stage and lymph node metastasis of colorectal cancer. LPS could promote the migration and invasion, which could be blocked by the neutralizing antibody IgG of VEGFR-3. And found that -159 nt to +65 nt was the crucial region of VEGFR-3 promoter. And detected that the NF-κB was important transcription factor for the VEGFR-3 promoter. And LPS could increase NF-κB binding to VEGFR-3 promoter and upregulated the expression of VEGFR-3 to exert biological functions. Conclusion: We have elucidated the relationship between LPS and the VEGFR-3 expression and revealed that VEGFR-3 play very important role in the process of LPS promoting the migration and invasion of colorectal cancer cells. Further illuminated the mechanism that LPS upregulated VEGFR-3 expression via increased NF-κB bind to the promoter of VEGFR-3.

scholarly journals Knockdown of SPOCK1 Inhibits the Proliferation and Invasion in Colorectal Cancer Cells by Suppressing the PI3K/Akt Pathway

2016 ◽  
Vol 24 (6) ◽  
pp. 437-445 ◽  
Author(s):  
Ping Zhao ◽  
Hai-Tao Guan ◽  
Zhi-Jun Dai ◽  
Yu-Guang Ma ◽  
Xiao-Xu Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Potential Therapeutic Target ◽  
Colorectal Cancer Cells ◽  
First Time ◽  
Proliferation In Vitro ◽  
Proliferation And Invasion ◽  
Hct116 Cells

Sparc/osteonectin, cwcv, and kazal-like domains proteoglycan (testican) 1 (SPOCK1), known as testican-1, were found to be involved in the development and progression of tumors. However, in colorectal cancer (CRC), the expression pattern of SPOCK1 and its functional role remain poorly investigated. In the present study, we explored the role of SPOCK1 in CRC. Our results demonstrated that SPOCK1 is overexpressed in CRC cell lines. SPOCK1 silencing significantly inhibited the proliferation in vitro and the tumor growth in vivo. Furthermore, SPOCK1 silencing significantly attenuated the migration/invasion by reversing the EMT process in CRC cells. Finally, knockdown of SPOCK1 obviously decreased the protein expression levels of p-PI3K and p-Akt in HCT116 cells. In total, our study demonstrated for the first time that knockdown of SPOCK1 inhibits the proliferation and invasion in CRC cells, possibly through the PI3K/Akt signaling pathway. Therefore, SPOCK1 may be a potential therapeutic target for the treatment of CRC.

scholarly journals Empty Spiracles Homeobox 2 (EMX2) Inhibits the Invasion and Tumorigenesis in Colorectal Cancer Cells

2017 ◽  
Vol 25 (4) ◽  
pp. 537-544 ◽  
Author(s):  
Yan Zhang ◽  
Gang Cao ◽  
Qing-gong Yuan ◽  
Jun-hui Li ◽  
Wen-Bin Yang
Keyword(s):  
Colorectal Cancer ◽  
Transcription Factor ◽  
Essential Role ◽  
Migration And Invasion ◽  
Human Colorectal Cancer ◽  
Potential Therapeutic Target ◽  
Colorectal Cancer Cells ◽  
Proliferation In Vitro

Empty spiracles homeobox 2 (EMX2) is a homeodomain-containing transcription factor that plays an essential role in tumorigenesis. However, to the best of our knowledge, the role of EMX2 in human colorectal cancer (CRC) is still unclear. Thus, the aim of this study was to investigate the expression and role of EMX2 in CRC. Our results demonstrated that the expression of EMX2 was greatly decreased in CRC tissues and cell lines. Overexpression of EMX2 significantly inhibited the proliferation in vitro and CRC tumor growth in nude mice. In addition, EMX2 also inhibited the migration and invasion of CRC cells. Mechanically, overexpression of EMX2 downregulated the expression levels of β-catenin, cyclin D1, and c-Myc in CRC cells. Taken together, our study demonstrates that EMX2 inhibits proliferation and tumorigenesis through inactivation of the Wnt/β-catenin pathway in CRC cells. Therefore, EMX2 may be a potential therapeutic target for the treatment of CRC.

scholarly journals ABCB1 and ABCG2 restricts the efficacy of gedatolisib (PF-05212384), a PI3K inhibitor in colorectal cancer cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Changfu Liu ◽  
Wenge Xing ◽  
Haipeng Yu ◽  
Weihao Zhang ◽  
Tongguo Si
Keyword(s):  
Colorectal Cancer ◽  
Atpase Activity ◽  
Cancer Cells ◽  
Cell Line ◽  
Abc Transporters ◽  
Expression Level ◽  
Colorectal Cancer Cell Line ◽  
Colorectal Cancer Cells ◽  
Mtt Assays

Abstract Background Overexpression of ABC transporters is a big challenge on cancer therapy which will lead cancer cells resistance to a series of anticancer drugs. Gedatolisib is a dual PI3K and mTOR inhibitor which is under clinical evaluation for multiple types of malignancies, including colorectal cancer. The growth inhibitory effects of gedatolisib on colorectal cancer cells have been specifically studied. However, the role of ABC transporters on gedatolisib resistance remained unclear. In present study, we illustrated the role of ABC transporters on gedatolisib resistance in colorectal cancer cells. Methods Cell viability investigations of gedatolisib on colorectal cancer cells were determined by MTT assays. The verapamil and Ko143 reversal studies were determined by MTT assays as well. ABCB1 and/or ABCG2 siRNA interference assays were conducted to verify the role of ABCB1- and ABCG2-overexpression on gedatolisib resistance. The accumulation assays of gedatolisib were conducted using tritium-labeled paclitaxel and mitoxantrone. The effects of gedatolisib on ATPase activity of ABCB1 or ABCG2 were conducted using PREDEASY ATPase Kits. The expression level of ABCB1 and ABCG2 after gedatolisib treatment were conducted by Western blotting and immunofluorescence assays. The well-docked position of gedatolisib with crystal structure of ABCB1 and ABCG2 were simulated by Autodock vina software. One-way ANOVA was used for the statistics analysis. Results Gedatolisib competitively increased the accumulation of tritium-labeled substrate-drugs in both ABCB1- and ABCG2-overexpression colorectal cancer cells. Moreover, gedatolisib significantly increased the protein expression level of ABCB1 and ABCG2 in colorectal cancer cells. In addition, gedatolisib remarkably simulated the ATPase activity of both ABCB1 and ABCG2, suggesting that gedatolisib is a substrate drug of both ABCB1 and ABCG2 transporters. Furthermore, a gedatolisib-resistance colorectal cancer cell line, SW620/GEDA, was selected by increasingly treatment with gedatolisib to SW620 cells. The SW620/GEDA cell line was proved to resistant to gedatolisib and a series of chemotherapeutic drugs, except cisplatin. The ABCB1 and ABCG2 were observed overexpression in SW620/GEDA cell line. Conclusions These findings suggest that overexpression of ABCB1 and ABCG2 may restrict the efficacy of gedatolisib in colorectal cancer cells, while co-administration with ABC transporter inhibitors may improve the potency of gedatolisib.

Analysis of oxaliplatin resistance in colorectal cancer cells by combined proteomics and phosphoproteomic

2020 ◽  
Vol 17 ◽  
Author(s):  
Rui Yang ◽  
Kunli Feng ◽  
Yanhong Cao ◽  
Hao Wang ◽  
Baolong Wang
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Protein Domain ◽  
Cancer Resistance ◽  
Kegg Pathways ◽  
Colorectal Cancer Cells ◽  
Hplc Fractionation ◽  
Hct116 Cells

Background: Oxaliplatin(Oxa) is a major chemotherapy drug for colorectal cancer. However, drug resistance is a major cause of treatment failure for late-stage colorectal cancer. Therefore, it is necessary to explore the mechanism of resistance to oxaliplatin in HCT116 colorectal cancer cells. Objective: Therefore, this study explored the mechanisms of HCT116 cells resistance to oxaliplatin by combining the results of proteomic and phosphoproteomic analyses. Method: In this study, first，we constructed oxaliplatin-resistant HCT116 cells, called HCT116/Oxa. Then, we conducted a quantitative study of phosphoproteomics in HCT116 and HCT116/Oxa cells via TMT labeling, bio-material-based PTM enrichment, HPLC fractionation, and LC-MS/MS analyses. At the same time, we applied TMT/iTRAQ labeling, HPLC fractionation, and LC-MS/MS to conduct proteomic and phosphoproteomic analyses of the cell lines. Finally, we analyzed the results from Gene Ontology (GO), protein domain, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using the 1.5 change rate as a meaningful change threshold. Results: Our analysis confirmed the previously described mechanisms of colon cancer resistance and revealed the important role of phosphorylation in drug resistance. Conclusion: Collectively, this study provides a new direction for the study of oxaliplatin resistance in colorectal cancer.

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