title: Apoptotic block in colon cancer cells may be rectified by lentivirus mediated overexpression of caspase-9.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.affiliation: Institute of Respiratory Diseases, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: D
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Gastrointestinal Surgery & Institute of Digestive Surgery, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal Surgery & Institute of Digestive Surgery, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Gastrointestinal Surgery & Institute of Digestive Surgery, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Gastrointestinal Surgery & Institute of Digestive Surgery, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Rui
authors.affiliation: Department of Gastrointestinal Surgery & Institute of Digestive Surgery, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: D
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Surgery & Institute of Digestive Surgery, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D017209:Apoptosis; D001706:Biopsy; D015153:Blotting, Western; D053453:Caspase 9 / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000201:enzymology / Q000473:pathology*; D016086:Lentivirus / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012334:RNA, Neoplasm / Q000235:genetics*; D012367:RNA, Viral; D012189:Retrospective Studies
chemical_list: D012334:RNA, Neoplasm; D012367:RNA, Viral; D053453:Caspase 9