Attenuation of vinblastine-induced apoptosis and degradation of I?B-? in breast cancer cell line by caspase-3 inhibitor / 中国病理生理杂志

ABSTRACT

AIM:To investigate the changes of apoptosis and activation of I??-? induced by vinblastine via the blockage of caspase-3 signal transduction pathway, and to explore the possible mechanism of signal transduction pathway involving in the vinblastine-induced apoptosis. METHODS: The breast cancer cell lines Bcap37 were treated with different concentrations of vinblatine dissolved in dimethyl sulphoxide (DMSO) or caspase-3 inhibitor (DEVD-CHO, 100 ?mol/L) for 3 h. The changes of the proliferation were detected by MTT methods. The apoptosis was determined by observing the internucleosomal DNA cleavage and PI staining, and the proteins of pro-caspase-3 and I??-? were detected by Western blotting methods. RESULTS: The results showed that vinblastine induced the pro-caspase-3 degradation. The significantly attenuation of vinblastine-induced apoptosis in breast cancer cell line by caspase-3 inhibitor DEVD-CHO was verified by MTT assay, internucleosomal DNA cleavage and flow cytometry PI staining analysis. The IC50 was 56.8 ?mol/L and 87.4 ?mol/L respectively for two groups. The inhibition of vinblastine-induced phosphorylated degradation of I??-? was also observed by DEVD-CHO. CONCLUSION: Based on these finding, vinblastine induces apoptosis in breast cancer cells via NF-??/I?? signal transduction pathway, which is co-operated by caspase signal pathway. Through the blockage of caspase pathway with caspase-3 inhibitor, vinblastine-induced apoptosis and the phosphorylated degradation of I??-? in breast cancer cells are suppressed greatly.