title: Resistance to chemotherapy-induced apoptosis via decreased caspase-3 activity and overexpression of antiapoptotic proteins in ovarian cancer.
abstract: OBJECTIVE
  Resistance to cisplatin is the main reason for treatment failure in ovarian cancer. Apoptosis is the main mechanism of action of most cancer chemotherapeutic agents. The apoptosis-associated proteins expressed in cisplatin-sensitive (A2780, COC1) and -resistant (A2780/DDP, COC1/DDP) ovarian cancer cell lines, as well as their effects on caspase-3 activity in these cells, were studied by reverse transcriptase polymerase chain reaction and Western blot analysis.
  
  
  METHODS
  The apoptotic ratios of A2780, COC1, A2780/DDP, and COC1/DDP cells after treatment with cisplatin were measured by flow cytometry.
  
  
  RESULTS
  Expression of Bcl-2 and Bcl-X(L) in A2780/DDP and COC1/DDP cells was significantly higher than that in A2780 and COC1 cells, respectively. Expression of Bax and Bcl-Xs did not differ in cisplatin-resistant and -sensitive cells. Caspase-3 activity was reduced markedly and apoptotic ratios were significantly lower in A2780/DDP and COC1/DDP cells than in A2780 and COC1 cells after treatment with cisplatin.
  
  
  CONCLUSIONS
  We conclude that overexpression of antiapoptotic proteins Bcl-2 and Bcl-X(L) and down-regulation of caspase-3 activity may be associated with cisplatin resistance in human ovarian cancer.
authors.affiliation: Division of Gynecological Oncology, Department of Obstetrics & Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, Hubei, PR China.
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Yang
authors.forename: Fang
authors.initials: F
authors.lastname: Zheng
authors.forename: Hui
authors.initials: H
authors.lastname: Xing
authors.forename: Qinglei
authors.initials: Q
authors.lastname: Gao
authors.forename: Wang
authors.initials: W
authors.lastname: Wei
authors.forename: Yunping
authors.initials: Y
authors.lastname: Lu
authors.forename: Shixuan
authors.initials: S
authors.lastname: Wang
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zhou
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.forename: Ding
authors.initials: D
authors.lastname: Ma
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004789:Enzyme Activation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000201:enzymology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D012313:RNA / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
chemical_list: D000970:Antineoplastic Agents; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D012313:RNA; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D002945:Cisplatin