摘要
目的探讨细胞外信号激酶(ERK)在紫杉醇引起的卵巢癌细胞调亡中的作用。方法用紫杉醇处理人卵巢上皮性腺癌细胞株Caov-3 and Skov-3,应用二氨基联苯染色,在显微镜下观察其凋亡。应用蛋白印迹法技术,用特异性识别双磷酸化ERK1/2的抗体,检测卵巢癌细胞经泰素作用后ERK1/2的活化情况。用MTT法检测PD98059对泰素引导的卵巢癌细胞毒性的影响。结果在80 nM泰素导致Caov-3 和Skov3细胞凋亡和ERK1/2激活,泰素作用9 h后,出现ERK的激活,15 h后活性最大。用100μM 的PD 98059 作用于不同药物浓度(60 nM 和80 nM)的泰素作用的细胞,细胞存活率显著降低(P <0.05)。结论泰素能激活卵巢癌Caov-3 和Skov3细胞ERK。抑制ERK的活性能提高Caov-3 和Skov3细胞对泰素的敏感性。阻断MEK1/ERK信号转导通路,可以增加泰素对卵巢癌的细胞毒作用。
Objective: To investigate the role of extracellular signal-regulated protein kinase (ERK) in Taxol-induced apoptosis in human ovarian carcinoma cells. Methods: Taxol-induced apoptosis was stained with DAPI and was assessed through microscope in Caov-3 and Skov-3 human epithelial adenocarcinoma ovarian cells. The activity of ERK1/2 was analyzed with phosphospecific antibodies directed against the dually phosphorylated, active forms of ERK1/2 by western blot. The effect of PD98059 on Taxol cytotoxicity to ovarian carcinoma cells was detected by MTT assay. Results: Taxol at 80 nM resulted in massive apoptosis , and led to strong activation of ERK. The ERK activation induced by Taxol occurred at 9 h after a treatment of Taxol and increased to the highest induction at 15 h. The effect of PD 98059 on ERK activity induced by Taxol was observed at the concentration of PD 98059 of 100 μM, in which a significantly decreasing rate of cell survival was observed after the addition of Taxol at 60 nM and 80 nM (P <0.05). Conclusions: Taxol activates the ERK signal pathway in human ovarian cancer cell lines Caov-3 and Skov3. Inhibition of ERK activity enhances the sensitivity of Caov-3 and Skov-3 cells to Taxol cytotoxity. Block of the MEK1/ERK pathway may potentiate the cytotoxic effect of Taxol on ovarian cancer cell.
出处
《中国现代医学杂志》
CAS
CSCD
2004年第19期1-5,共5页
China Journal of Modern Medicine
基金
This project was supported by Heilongjiang Province government natural science funds (No:D03-55) and Heilongjiang Province sanitary bureau scientific funds (No:2003-003)
关键词
卵巢癌细胞
细胞外信号调节激酶
细胞毒性
泰素
凋亡
extracellular signal-regulated kinases
taxol
apoptosis
human ovarian carcinoma cells