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Acta Gastroenterol Belg. 2013 Dec;76(4):372-80.

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

Author information

1
Institute of Respiratory Diseases, West China Hospital, Sichuan University, Chengdu 610041, PR China.
2
Department of Gastrointestinal Surgery & Institute of Digestive Surgery, West China Hospital, Sichuan University, Chengdu 610041, PR China.

Abstract

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 caspase-9 in normal colon mucosa, adenoma and cancer, investigating the relationship between its expression and clinico-pathological characteristics. Secondly, overexpression of caspase-9 was established 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-regulation of caspase-9 expression is more common in poorly differentiated cancers (P < 0.05). Concerning cell lines, overexpression cell groups showed higher expression of caspase-9, poorer colony formation and slower cell proliferation. In terms of apoptosis related indicators, caspase-9 overexpression leads to higher apoptosis rate and GO/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.

PMID:
24592539
[Indexed for MEDLINE]
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