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

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.

• Authors: D Xu, C Wang, X Shen, Y Yu, Y Rui, D Zhang, Z Zhou
• Journal: Acta gastro-enterologica Belgica (Acta Gastroenterol Belg) Vol. 76 Issue 4 Pg. 372-80 (Dec 2013) ISSN: 1784-3227 [Print] Belgium
• PMID: 24592539 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Neoplasm
• RNA, Viral
• Caspase 9

Topics

• Apoptosis
• Biopsy
• Blotting, Western
• Caspase 9 (biosynthesis, genetics)
• Cell Line, Tumor
• Cell Proliferation
• Colonic Neoplasms (enzymology, genetics, pathology)
• Female
• Flow Cytometry
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• In Situ Nick-End Labeling
• Intestinal Mucosa (enzymology, pathology)
• Lentivirus (genetics)
• Male
• Middle Aged
• Polymerase Chain Reaction
• RNA, Neoplasm (genetics)
• RNA, Viral
• Retrospective Studies