αvβ6-ERK pathway participates in norcantharidin-induced apoptosis of HT-29 colon cancer cells |
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| Authors: | ZHANG Qi HU Yan-yan PENG Cheng NIU Wei-bo LIU En-yu HE Zhao-bin ZHAO Chuan-zong NIU Jun |
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| Institution: | 1. Department of Hematology and Oncology, The Second Hospital of Shandong University, Jinan 250033, China;
2. Department of Geriatric Medicine,Qilu Hospital, Shandong University, Jinan 250012, China;
3. Department of Hepatobiliary, Qilu Hospital, Shandong University, Jinan 250012, China |
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| Abstract: | AIM: To investigate the pharmacological mechanism of norcantharidin (NCTD)-induced apoptosis of HT-29 colon cancer cells. METHODS: Hoechst 33258 staining was used to analyze the apoptosis of HT-29 cells treated with NCTD. The effects of NCTD on the expression of integrin in HT-29 cells were determined by flow cytometry. The effects of several functional blocking antibodies on HT-29 cells were detected by MTT method. The expression and the phosphorylation of mitogen activated protein kinases (MAPKs) in HT-29 cells were measured by Western blotting. Co-immunoprecipitation assay was used to detect the activity of αvβ6-extracellular signal-regulated kinase (ERK) direct linkage in HT-29 cells.RESULTS: NCTD induced the apoptosis of HT-29 colon cancer cells. The expression of integrin αvβ6 in HT-29 cells treated with NCTD was reduced, but the expression of αvβ3 and αvβ5 was not changed. A function-blocking antibody to αvβ6,10D5,strengthened the growth inhibitory effect of NCTD on HT-29 cells ,but LM609 (a function-blocking antibody to αvβ3) and P1F6 (a function-blocking antibody to αvβ5) did not. The level of phosphorylated ERK (p-ERK) was decreased substantially after treated with NCTD in a dose-and time-dependent manner. NCTD also affected the association of αvβ6 and ERK. CONCLUSION: NCTD decreases the expression of integrin αvβ6 and interferes with the phosphorylation of ERK. As a result, the formation of αvβ6-ERK direct linkage is affected and the signal transduction mediated by αvβ6 is disturbed. The mechanism of NCTD-induced HT-29 cell apoptosis is involved in the αvβ6-ERK signaling pathway. |
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| Keywords: | Norcantharidin Integrin αvβ6 Apoptosis Colonic neoplasms |
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