[Relationship between expression of apoptosis-associated proteins and caspase-3 activity in cisplatin-resistant human ovarian cancer cell line].
OBJECTIVE
Cisplatin-based chemotherapy is an important way for treatment of ovarian cancer, but resistance to cisplatin is one of the reasons of treatment failure of ovarian cancer. This study was designed to investigate the relationship between apoptosis-associated proteins and caspase-3 activity as well as their effects on chemoresistance in human ovarian cancer cell lines.


METHODS
The expression of apoptosis-associated proteins (bcl-2, bcl-xL, bax, bcl-xs), the activity of caspase-3 and cleavage of poly ADP-ribose polymerase (PARP) were determined with Western blot analysis in the cisplatin-resistant cell (COC1/DDP) and cisplatin-sensitive human ovarian cancer cell (COC1). The apoptotic ratios of COC1 and COC1/DDP were measured with flow cytometry after treated with different concentration of cisplatin.


RESULTS
The expression of bcl-2 and bcl-XL in COC1/DDP cell was significantly higher than that in COC1 cell, whereas the expression of bax showed no change in COC1/DDP and COC1. There was no bcl-xs expression in both COC1 and COC1/DDP cells. The activity of caspase-3, the amount of PARP fragments, and apoptotic ratio in COC1/DDP reduced much more than COC1 did after treated with cisplatin.


CONCLUSIONS
Cisplatin-resistance in human ovarian cancer cell lines may associated with the overexpression of anti-apoptotic protein bcl-2 and downregulation of caspase-3 activity, but not associated with the expression of bax and bcl-xs.
Yang
Xiao-kui
XK
Department of Obstetrics & Gynecology, Tongji Hospital, Tongji Medical College, University of Huazhong Science and Technology, Wuhan 430030, P. R. China.
Zheng
Fang
F
Chen
Jian-hua
JH
Gao
Qing-lei
QL
Lu
Yun-ping
YP
Wang
Shi-xuan
SX
Wang
Chang-yu
CY
Ma
Ding
D
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis*; D002945:Cisplatin / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000096:biosynthesis*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000473:pathology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D003598:Cytoskeletal Proteins; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D002945:Cisplatin