Silibinin Inhibits TGF-β-induced MMP-2 and MMP-9 Through Smad Signaling Pathway in Colorectal Cancer HT-29 Cells

Background: Metastasis of cancer cells is the primary responsible for death in patients with colorectal cancer (CRC). Transforming growth factor-β (TGF-β)-induced matrix metalloproteinases (MMPs) are essential for the metastasis process. Silibinin is a natural compound extracted from the Silybum marianum that exhibits anti-neoplastic activity in cancer cell lines. In this study, we evaluated the effects of silibinin on MMP-2 and MMP-9 induced by TGF-β in human HT-29 CRC cell line and the potential mechanism underlying the effects. Methods: The present in vitro study was done on the HT-29 cell line. The HT-29 cell line was cultured in RPMI1640 and exposed to TGF- β (5 ng/ml) in the absence and presence of different concentrations of silibinin (10, 25, 50, and 100 μM). The effect of silibinin on HT-29 cell viability was measured with the MTT assay. A real-time polymerase chain reaction (Real-Time PCR) determined the relative mRNA expression of MMP-2 and MMP-9. Western blotting was employed to examine MMP-2 and MMP 9 protein expression and Smad2 phosphorylation. Results: Silibinin inhibits cell viability of HT-29 cell line at 24 hours in a dose-dependent manner. TGF-β increased the mRNA and protein expression of MMP-2, MMP-9, and phosphorylated Smad2 compared to controls. Pharmacological inhibition with silibinin markedly blocked TGF-β–induced MMP-2 and MMP-9 mRNA and protein expression and Smad2 phosphorylation. Conclusion: Silibinin decreased the cell viability of HT-29 cancer cells in a dose-dependent manner. Silibinin also inhibited TGF-β-stimulated MMP-2 and MMP-9 expression in HT-29 cells, possibly mediated with the Smad2 signaling pathway.

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Scaphium affine Ethanol Extract Induces Anoikis by Regulating the EGFR/Akt Pathway in HCT116 Colorectal Cancer Cells

Frontiers in Oncology ◽

10.3389/fonc.2021.621346 ◽

2021 ◽

Vol 11 ◽

Author(s):

Hye Won Kawk ◽

Gun-He Nam ◽

Myeong Jin Kim ◽

Sang-Yong Kim ◽

Young-Min Kim

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Cell Line ◽

Hct116 Cell ◽

Akt Pathway ◽

Dependent Manner ◽

Anticancer Effects ◽

Colorectal Cancer Cells ◽

Dose Dependent

Scaphium affine ethanol extracts (SAE) is a species that has been shown to contain various physiological effects; however, its anticancer effects have yet to be revealed. We qualitatively evaluated β-sitosterol in SAE through high-performance liquid chromatography (HPLC). The cytotoxicity in HCT116 and HT29 colorectal cancer cells and CCD841 normal colon cells was confirmed through WST-1 assays. Selective cytotoxicity was observed in colorectal cancer cells, with greater cytotoxicity demonstrated in the HCT116 cell line. As such, the HCT116 colorectal cell line was selected for subsequent experiments. After HCT116 cells were treated with SAE, it was confirmed that the apoptosis rate was increased in a SAE dose-dependent manner through Annexin V assay. SAE further showed dose-dependent suppression of invasion through invasion assays. Anoikis induction through the EGFR/Akt pathway in HCT116 colorectal cancer cells was confirmed by Western blotting. The tumor suppressive effects of SAE was assessed in vivo using a xenograft model of human HCT116 colorectal cancer cells. As a result, we confirmed that SAE decreased tumor size in a dose-dependent manner and that p-EGFR and cleaved-caspase 3 in tumors were also regulated in a dose-dependent manner. This study showed that SAE, by containing β-sitosterol with proven anticancer effects, induces anoikis through the EGFR/Akt pathway in HCT116 colorectal cancer cells both in vitro and in vivo.

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Targeted inhibition of GRP78 by HA15 promotes apoptosis of lung cancer cells accompanied by ER stress and autophagy

Biology Open ◽

10.1242/bio.053298 ◽

2020 ◽

Vol 9 (11) ◽

pp. bio053298

Author(s):

Jingjing Wu ◽

Youqile Wu ◽

Xuemei Lian

Keyword(s):

Lung Cancer ◽

Protein Expression ◽

Cell Viability ◽

Er Stress ◽

Cancer Cells ◽

Lung Tumor ◽

Lung Cancer Cells ◽

Dependent Manner ◽

Mice Model ◽

Targeted Inhibition

ABSTRACTThis study investigated the pathophysiological role of GRP78 in the survival of lung cancer cells. Lung cancer patient data from public databases were used to analyze the expression of GRP78 and its influence on prognoses. In vivo, GRP78 protein expression was analyzed in an established urethane-induced lung tumor mouse model. In vitro, the effects of targeted inhibition of GRP78 by HA15 in lung cancer cells were assessed, with cell viability analyzed using a CCK-8 assay, cell proliferation using an EdU assay, apoptosis and cell cycle using flow cytometry, subcellular structure using electron microscopy, and relative mRNA and protein expression using RT-PCR, western blotting or immunofluorescence assays. The results showed that GRP78 was highly expressed in the lung tissue of lung cancer mice model or patients, and was associated with a poor prognosis. After inhibition of GRP78 in lung cancer cells by HA15, cell viability was decreased in a dose- and time-dependent manner, proliferation was suppressed and apoptosis promoted. Unfolded protein response signaling pathway proteins were activated, and the autophagy-related proteins and mRNAs were upregulated. Therefore, targeted inhibition of GRP78 by HA15 promotes apoptosis of lung cancer cells accompanied by ER stress and autophagy.

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PLAC1 Enhances Metastatic Potential and is Associated with PI3K/AKT/NF-κB Signaling Pathway in Colon Cancer

10.21203/rs.2.15971/v1 ◽

2019 ◽

Author(s):

JIachi Ma ◽

Shoukai Zhang ◽

Danru Liang ◽

Lei Li ◽

Jun Du ◽

...

Keyword(s):

Colorectal Cancer ◽

Endothelial Cells ◽

Cancer Cells ◽

Umbilical Vein ◽

Metastatic Potential ◽

Dependent Manner ◽

Human Colorectal Cancer ◽

Colorectal Cancer Cells ◽

Metastatic Process ◽

Ht 29

Abstract Background: To better explore the underlying mechanism of liver metastatic formation by placenta-specific protein 1 (PLAC1) in human colorectal cancer, we investigated the proliferation, invasion and angiogenic capabilities of human colorectal cancer cell lines with different liver metastatic potentials as well as the mechanism of action of PLAC1 in the metastatic process. Methods: The expression of PLAC1 was detected by reverse transcriptase PCR, western blot and real-time PCR. The effect of PLAC1 on metastatic potential was determined by proliferation, invasion, and angiogenesis assays, including an in vitro coculture system consisting of cancer cells and vascular endothelial cells that were used to detect the relationship between cancer cells and angiogenesis. In addition, we also determined PLAC1 downstream targets that preferentially contribute to the metastatic process. Results: PLAC1 was expressed in HT-29, WiDr and CaCo-2 colorectal cancer cells but not in Colo320 colorectal cancer cells. PLAC1 could not only significantly enhance the proliferation of CoLo320 and human umbilical vein endothelial cells (HUVECs) but could also promote the invasion of CoLo320 cells. The angiogenesis of HUVECs was enhanced by PLAC1 in a dose-dependent manner. In cocultured systems, angiogenesis was significantly increased by coculture with HT-29 cells. In addition, PLAC1 could promote angiogenesis in coculture with HT-29 cells. Furthermore, PLAC1-enhanced metastatic potential of colorectal cancer cells was dependent on activation of the PI3K/Akt/NF-κB pathway. Conclusions: The activation of PI3K/Akt/NF-κB signaling by PLAC1 may be critical for the metastasis of colorectal cancer cells. According to our results, we suggest that modification of PLAC1 function might be a promising new therapeutic approach to inhibit the aggressive spread of colorectal cancer.

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MK886 Induced Apoptosis in HL-60 Cells Via Inhibition mPGES-1 Expression and Down-Regulation Prostaglandin E2 Synthesize.

Blood ◽

10.1182/blood.v114.22.4824.4824 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4824-4824

Author(s):

Yiqing Li ◽

Songmei Yin ◽

Shuangfeng Xie ◽

Danian Nie ◽

Liping Ma ◽

...

Keyword(s):

Cell Proliferation ◽

Protein Expression ◽

Prostaglandin E2 ◽

Cell Line ◽

Caspase 3 ◽

Leukemia Cell ◽

Leukemia Cell Line ◽

Dependent Manner ◽

Pge2 Synthesis ◽

Dose Dependent

Abstract Abstract 4824 Recent studies have shown that prostaglandin E2 (PGE2) may play a key role in the tumorigenesis and tumor development. Membrane-bound prostaglandin E2 synthase-1 (mPGES-1), an inducible enzyme that acts downstream of cyclooxygenase (COX) and specifically catalyzes the conversion of prostaglandin H2 (PGH2) to PGE2, was over-expression in a variety of solid tumor cells and tissues such as nonsmall-cell lung cancer, colon carcinoma, gastric carcinoma and breast cancer. MK886, a small molecular inhibitor, is a reasonable potency as an inhibitor of mPGES-1 in vitro experiment. In this study, we examined effects of MK886 on expression of mPGES-1 and PGE2 synthesis in human acute myeloid leukemia cell line (HL-60), observed cell proliferation and apoptosis after 24-h treatment with MK886, and tried to explore the possible mechanisms by checking some protein belong AKT cell singling pathway such as P-AKT, Bax and Bcl-2. We found that the expression levels of mPGES-1 mRNA and protein were higher in HL-60 cells than in normal mononuclearcells (MNC). MK886 inhibited mPGES-1 mRNA and protein expression and reduced PGE2 secretion in HL-60 cells in a dose-dependent manner. The cell proliferation was inhibited and the IC50 was 132.16μmol/L. With the increase of MK886 concentration, the cell apoptosis rate assayed by flow cytometry increased and the apparent apoptotic bodies increased when staining by Hoechst 33258. After treated with MK886 for 24h, protein was extracted and assayed by western blot. The results showed that the expression levels of P-AKT, Bcl-2 and c-myc decreased while the Bax protein expression increased in a dose-dependent manner. The caspase-3 activity, determined by colorimetric detection, also increased dose-dependently. These results indicated that mPGES-1 over-expressed in leukemia cell line HL-60, MK886 could induce apoptosis in HL-60 cells via reducing mPGES-1 expression and PGE2 synthesis dose-dependently, thereby regulate the AKT pathway including Bcl-2 family and the activity of caspase-3. It suggested that mPGES-1 inhibitor might emerge as an important therapeutic tool for leukemia treatment. Disclosures: No relevant conflicts of interest to declare.

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IKKα as a potential novel target for treatment of colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.174 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 174-174

Author(s):

Jean A. Quinn ◽

Meera Patel ◽

Kathryn AF Pennel ◽

Dustin Flanagan ◽

Paul G. Horgan ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Viability ◽

Mouse Models ◽

Dependent Manner ◽

Cancer Specific Survival ◽

Similar Reduction ◽

Novel Target ◽

Dose Dependent ◽

Tumour Differentiation

174 Background: Colorectal cancer (CRC) is a heterogeneous disease leading to different survival outcomes for patients with the same stage of disease. The non-canonical NF-κB pathway has been shown to have a key role in tumorigenesis, and the aim of this study was to investigate the role of IKKα, the main catalytic component of this pathway in CRC. Methods: A tissue microarray was retrospectively constructed from a patient cohort (1033) with stage I-III CRC who underwent surgery. IHC was utilised to examine cytoplasmic and punctate IKKα expression and determine any association with clincopathological features and cancer specific survival (CSS). To assess IKKα inhibition, organoids were prepared from wild type (WT) mouse colon, mouse models of CRC (Apc and Apc.KRAS.pT53.TGFbR2 (AKPT)) and patient derived human organoids. These were treated with an IKKα inhibitor, SU1433 and organoid size and cell viability assessed. Results: High cytoplasmic expression of IKKα was associated with increasing T stage (p = 0.012), poor tumour differentiation (p = 0.010), tumour necrosis (p = 0.013) and low proliferation status (p = 0.013) but was not associated with CSS. High punctate IKKα expression associated with tumour differentiation (p = 0.001), necrosis (p = 0.004), proliferation (p = 0.044) and MMR competence (p < 0.001) and was also significantly associated with reduced CSS (HR1.20 95%CI 1.02-1.42, p < 0.001). SU1433 did not significantly impact on WT (C57/B16) organoid viability up to a concentration of 1 uM, however organoid size and cell viability was significantly reduced in a dose dependent manner in organoids from both Apc and AKPT mouse models. A similar reduction was observed in patient derived human organoids. Conclusions: Punctate IKKα expression was associated with poor cancer specific survival in CRC patients, and inhibition with SU1433, impacted on CRC mouse and patient derived human organoid size and cell viability. These results suggest that, following further investigation and confirmation, IKKα may be employed as a novel therapeutic target in CRC.

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Placenta-Specific Protein 1 Enhances Liver Metastatic Potential and is Associated with the PI3K/AKT/NF-κB Signaling Pathway in Colorectal Cancer

10.21203/rs.2.24480/v2 ◽

2020 ◽

Author(s):

Jiachi Ma ◽

Lei Li ◽

Jun Du ◽

Chengwu Pan ◽

Chensong Zhang ◽

...

Keyword(s):

Colorectal Cancer ◽

Endothelial Cells ◽

Cancer Cells ◽

Metastatic Potential ◽

Specific Protein ◽

Dependent Manner ◽

Human Colorectal Cancer ◽

Colorectal Cancer Cells ◽

Metastatic Process ◽

Ht 29

Abstract Abstract Background: To better explore the underlying mechanism of liver metastatic formation by placenta-specific protein 1 (PLAC1) in human colorectal cancer, we investigated the proliferation, invasion and angiogenic capabilities of human colorectal cancer cell lines with different liver metastatic potentials as well as the mechanism of action of PLAC1 in the metastatic process. Methods: The expression of PLAC1 was detected by reverse transcriptase PCR, western blot and real-time PCR. The effect of PLAC1 on metastatic potential was determined by proliferation, invasion, and angiogenesis assays, including an in vitro coculture system consisting of cancer cells and vascular endothelial cells that were used to detect the relationship between cancer cells and angiogenesis. In addition, we also determined PLAC1 downstream targets that preferentially contribute to the metastatic process. Results: PLAC1 was expressed in HT-29, WiDr and CaCo-2 colorectal cancer cells but not in Colo320 colorectal cancer cells. PLAC1 not only enhanced significantly the proliferation of CoLo320 and human umbilical vein endothelial cells (HUVECs), but also promoted the invasion of CoLo320 cells. The angiogenesis of HUVECs was enhanced by PLAC1 in a dose-dependent manner. In cocultured systems, angiogenesis was significantly increased by coculture with HT-29 cells. In addition, PLAC1 could promote angiogenesis in coculture with HT-29 cells. Furthermore, PLAC1-enhanced metastatic potential of colorectal cancer cells was dependent on activation of the PI3K/Akt/NF-κB pathway. Conclusions: The activation of PI3K/Akt/NF-κB signaling by PLAC1 may be critical for the metastasis of colorectal cancer cells. According to our results, we suggest that modification of PLAC1 function might be a promising new therapeutic approach to inhibit the aggressive spread of colorectal cancer.

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Inhibition of Colorectal Cancer Cells HT-29 by Secretome and Extraction of Human Umbilical Cord Wharton’s Jelly Stem Cells

10.21203/rs.3.rs-142535/v1 ◽

2021 ◽

Author(s):

Mahdieh Farhoudi Sefidan Jadid ◽

Parisa Emami ◽

Pouya Goleij ◽

Vahidreza Karamad ◽

Afshin Khorrami ◽

...

Keyword(s):

Colorectal Cancer ◽

Stem Cells ◽

Cancer Cells ◽

Cell Line ◽

Conditioned Medium ◽

Umbilical Cord ◽

Human Umbilical Cord ◽

Apoptosis Induction ◽

Cell Lysate ◽

Ht 29

Abstract Background and aim: Colorectal cancer (CC) is aggressive cancer and the major cause of death worldwide that need the development of novel and effective therapeutic methods. Recently suggested that the human Wharton’s jelly stem cells (hWJSCs) have an anti-proliferation activity against of several cancer cells through apoptosis induction. Therefore, this study aimed to investigate the effects of conditioned medium and cell lysate of human umbilical cord hWJSCs against the HT-29 cancer cell line and mechanisms of apoptosis induction.Methods: In this study, the hWJSCs conditioned medium and cell lysate were prepared from 10 human umbilical cord samples. The effects of hWJSCs conditioned medium and cell lysate were evaluated on the viability, migration, invasion, and apoptosis of HT-29 CC cell line. The expression of apoptosis related BAX, BCL2, SMAC, SURVIVIN, and Cas9 genes were evaluated in CC cells treated with hWJSCs conditioned medium and cell lysate.Results: We observed that conditioned medium and cell lysate of hWJSCs decrease CC cells viability, proliferation, migration, and invasion in a concentration- and time-dependent manner. Moreover, conditioned medium and cell lysate increased apoptosis rate of CC cells, which can be due to increase BAX, SMAC, and Cas9 genes, as well as decrease BCL2 and SURVIVIN genes.Conclusions: Our study suggest that conditioned medium and cell lysate of hWJSCs can inhibit CC cells through induction of apoptosis. However, further studies on are required to more accurate results.

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FGF21 Ameliorates Hepatic Fibrosis by Multiple Mechanisms

10.21203/rs.3.rs-418625/v1 ◽

2021 ◽

Author(s):

Fanrui Meng ◽

Mir Hassan Khoso ◽

Kai Kang ◽

Qi He ◽

Yukai Cao ◽

...

Keyword(s):

Protein Expression ◽

Western Blot ◽

Hepatic Fibrosis ◽

Blot Analysis ◽

Western Blot Analysis ◽

Cell Model ◽

Dependent Manner ◽

Rt Pcr ◽

Mrna And Protein Expression ◽

Dose Dependent

Abstract Previous study reports that FGF21 could ameliorate hepatic fibrosis, but its mechanisms have not been fully investigated. In this study, three models were used to investigate the mechanism by which FGF21 alleviates liver fibrosis. CCL4 and DMN were respectively used to induce hepatic fibrosis animal models. Our results demonstrated that liver index and liver function were deteriorated in both models. HE and Masson’s staining showed that the damaged tissue architectonics were observed in the mice of both models. Treatment with FGF21 significantly ameliorated these changes. ELISA analysis showed that the serum levels of IL-1β, IL-6 and TNF-α were significantly elevated in both models. However, administration of FGF21 significantly reduced these inflammatory cytokines. RT-PCR and Western blot analysis showed that mRNA and protein expression of collagenI, α-SMA and TGF-β were significantly decreased by treatment with FGF21. PDGF-BB stimulant was used to establish the experimental cell model in HSCs. RT-PCR and Western blot analysis demonstrated that the expression of collagenI and α-SMA were significantly upregulated by this stimulant in model group. Interestingly, our results showed that mRNA and protein expression of leptin were also significantly induced in PDGF-BB treated HSCs. Administration of FGF21 could significantly reduce leptin expression in a dose dependent manner and these effects were reversed in siRNA (against β-klotho) transfected HSCs. Furthermore, the leptin signaling pathways related protein p-ERK/t-ERK, p-STAT3/STAT3 and TGF-β were significantly downregulated by FGF21 treatment in a dose dependent manner. The expression of SOCS3 and Nrf-2 were enhanced by treatment with FGF21. The underlying mechanism may be that FGF21 regulates leptin-STAT3 axis via Nrf-2 and SOCS3 pathway in activated HSCs.

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Pharmacodynamic analysis of receptor tyrosine kinase (RTK) activity reveals differential target inhibition in skin and tumor in a phase I study of advanced colorectal cancer patients treated with AEE788

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.3601 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 3601-3601

Author(s):

D. W. Davis ◽

J. Huang ◽

W. Liu ◽

L. Xiao ◽

A. Thomas ◽

...

Keyword(s):

Colorectal Cancer ◽

Endothelial Cell ◽

Cancer Patients ◽

Advanced Colorectal Cancer ◽

Post Treatment ◽

Dependent Manner ◽

Colorectal Cancer Patients ◽

Dose Dependent ◽

Ht 29

3601 Background: AEE788 (AEE) is an oral inhibitor against tyrosine kinases and has an IC50 of < 100 nM against EGFR and VEGFR-2. This PD study investigated the effects of AEE on its targets in vitro and in biopsies from advanced colorectal cancer patients. Methods: HUVECs and HT-29 cells were incubated with AEE for 4h at 0–1 mM. 22 pts were treated at doses of 25 (n=4), 50 (n=3), 100 (n=4), 250 (n=1), 300 (n=4), and 400 mg (n=6) mg/day in 28-day cycles. No major clinical respones were observed. Wound-induced paired skin biopsies were performed on days -8, -1, 22, 29. Tumor biopsies were obtained before and 28 days post-treatment. Evaluable paired skin and tumor samples were available in 18 and 14 patients respectively. The effects of AEE on pKDR, pEGFR, AKT, Ki67, and apoptosis were analyzed by laser scanning cytometry (LSC). Wilcoxon signed rank test and Spearman correlation were used to compare biomarker changes post-treatment and correlation with dose, respectively. Results: In vitro, AEE treatment resulted in a dose-dependent inhibition of pKDR and pEGFR with inhibition of 65% and 63% at 1 mM in HUVECs and HT-29 cells, respectively. pKDR levels increased in response to AEE treatment in HT-29 cells. In skin, AEE increased basal levels of pKDR (p=0.03) post-treatment. AEE increased AKT (p=0.02) and EGFR (p=0.01) in a dose-dependent manner. In wound-induced skin pairs, AEE significantly inhibited endothelial cell pKDR/KDR (ratio) in a dose-dependent manner (p=0.02). In tumors, AEE increased pKDR expression (p=0.05) and was dose-dependent (p=0.06). Tumor endothelial cell pKDR levels decreased (avg. 47%) after AEE treatment (p=0.08). Furthermore, levels of Ki67 increased (p=0.08) and no significant effects were observed on pEGFR or apoptosis at any dose level in post-treatment samples. Conclusions: LSC quantitative analysis confirmed the target inhibition of AEE in vitro and in wound-induced skin pairs. The lack of significant target inhibition in tumors is consistent with the lack of clinical activity of AEE in this cohort of patients. Quantifying pKDR/KDR in wound-induced skin pairs may serve as a surrogate for assessing the activity of an angiogenesis inhibitor such as AEE. [Table: see text]

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Effect of AbGn-7, a glycotope-specific monoclonal antibody, on apoptosis in colon cancer cells and tumor growth in xenograft models

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e15118 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e15118-e15118

Author(s):

S. Lin ◽

E. Chiang ◽

Y. Tsai ◽

S. Lee ◽

B. Kuo ◽

...

Keyword(s):

Colorectal Cancer ◽

Monoclonal Antibody ◽

Colon Cancer ◽

Monoclonal Antibodies ◽

Cancer Cells ◽

Parp Cleavage ◽

Potential Candidate ◽

Dependent Manner ◽

Colon Cancer Cells ◽

Dose Dependent

e15118 Background: While clinical benefit against colorectal cancer has been observed with therapeutic monoclonal antibodies such as bevacizumab, cetuximab and panituzumab, the death rate of advanced colorectal cancer remains high that warrants further development of more potent therapeutics. Methods: A cell-based immunization approach was used to generate monoclonal antibodies against targets expressed on human colorectal cancer cells. A chimeric monoclonal antibody, AbGn-7, was selected and evaluated for the potential clinical use to treat colorectal cancer. Results: Expression of AbGn-7 antigen: Carbohydrate competition assay demonstrated that AbGn-7 recognizes a Lewis-A-like carbohydrate antigen (AbGn-7 antigen). Immunohistochemical studies showed that AbGn-7 antigen is expressed in colorectal cancer tissue. No significant binding could be detected in non-tumor tissues except in the epithelia of GI track. Effector function of AbGn-7: AbGn-7 triggered dose-dependent apoptosis in COLO 205 colon cancer cell. In addition, AbGn-7 elicited potent complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) in a dose-dependent manner. Molecular mechanism of apoptosis induced by AbGn-7: Tunel assay, PARP cleavage assay as well as caspase inhibitor studies demonstrated that AbGn-7 induced apoptosis in COLO 205 colon cancer cells via a caspase-independent pathway. Xenograft study: AbGn-7 alone, or in combination with 5FU-Leucovorin, effectively inhibited the growth of COLO 205 xenograft in SCID mice and prolonged their survival. Conclusions: The results of the present study suggest that AbGn-7 is a potential candidate for effective treatment of colorectal cancer. [Table: see text]

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