Role of ERK1/2 kinase in cisplatin-induced apoptosis in human ovarian carcinoma cells.
OBJECTIVE
To investigate the role of extracellular regulated kinase (ERK1/2) pathway in cisplatin-induced apoptosis in human ovarian carcinoma cells.


METHODS
Cisplatin-induced apoptosis were stained with DAPI and was assessed microscopically in human epithelial adenocarcinoma ovarian cell line SKOV3 cells. ERK activation was determined by Western blotting using an anti-phospho-ERK antibody to detect ERK activity. The effect of PD98059 on ERK activity induced by cisplatin was detected by MTT assay.


RESULTS
Marked apoptosis of SKOV3 cells resulted from 48 hours treatment with 20 microg/mL cisplatin. Strong activation of ERK was led to by 15 microg/mL cisplatin. Dose response and time course of cisplatin induced apoptosis in SKOV3 cells. Cisplatin-induced ERK activation occurred at 12 hours and increased to highest induction at 24 hours by Western blotting. The effect of PD 98059 on ERK activity induced by cisplatin at the concentration of 100 micromol/L PD 98059. Statistically significant decreased in cell survival were observed with 100 micromol/L PD 98059 at 15 and 20 microg/mL cisplatin (P < 0.05).


CONCLUSIONS
Cisplatin activates the ERK signaling pathway in ovarian cancer cell line SKOV3. Inhibition of ERK activity enhances sensitivity to cisplatin cytotoxity in ovarian cancer cell line SKOV3. Evaluation of ERK activity could be useful in predicting which ovarian cancer will response most favorably to cisplatin therapy.
Wei
Shu-Qin
SQ
Department of Obstetrics and Gynecology, First Clinical College, Harbin Medical University, Harbin 150001. weishuqin@hotmail.com
Sui
Li-Hua
LH
Zheng
Jian-Hua
JH
Zhang
Guang-Mei
GM
Kao
Yan-Lin
YL
D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000473:pathology*; D015398:Signal Transduction
D000970:Antineoplastic Agents; D005419:Flavonoids; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D002945:Cisplatin; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one