Apoptotic block in colon cancer cells may be rectified by lentivirus mediated overexpression of caspase-9

Background and aim : At present, the inhibition of apoptosis during pathogenesis of colorectal cancer is widely recognized while the role of caspase-9 in this process remains controversial. We aimed to investigate the differential expression of caspase-9 and evaluate the therapeutic potential of expression intervention in this study. Methods : We first examined the different expression of cas- pase-9 in normal colon mucosa, adenoma and cancer, investigating the relationship between its expression and clinico-pathological characteristics. Secondly, overexpression of caspase-9 was estab- lished in colon cancer cell lines by lentivirus infection to study the changes in growth, proliferation and apoptosis. Results : Compared with normal colon mucosa, the expression of caspase-9 was higher in adenoma while lower in cancer both at mRNA and protein level (P < 0.05). In addition, the down-regula- tion of caspase-9 expression is more common in poorly differenti- ated cancers (P < 0.05). Concerning cell lines, overexpression cell groups showed higher expression of caspase-9, poorer colony for- mation and slower cell proliferation. In terms of apoptosis related indicators, caspase-9 overexpression leads to higher apoptosis rate and G0/G1 arrest, while up-regulating the expression of caspase-3 (P<0.05). Interestingly, down-regulation of carcinoembryonic antigen secretion was also observed in caspase-9 overexpression cells (P < 0.05). Conclusion : The change of caspase-9 expression from colon mucosa, adenoma to cancer suggested it may be involved in the carcinogenesis of colon cancer. The overexpression of caspase-9 exhibits an inhibitory role in cancer growth and proliferation while promoting apoptosis. However, a non-apoptotic role of caspase-9 facilitating differentiation was also implied. (Acta gastroenterol. belg., 2013, 76, 372-380).