Ma Xiang-Yi, Wang Shi-Xuan, Liu Yan, Liu Rong-Hua, Lu Yun-Ping, Ma Ding
Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
Ai Zheng. 2007 Apr;26(4):367-70.
BACKGROUND & OBJECTIVE: Previous researches confirmed that the mammalian target of rapamycin (mTOR) plays an important role in the tumorigenesis and development of malignant tumors. This study was to investigate the effect of rapamycin, a selective inhibitor of mTOR, combined paclitaxel on the apoptosis of ovarian cancer cell lines A2780 and SKOV3, and explore the molecular mechanism.
A2780 and SKOV3 cells were treated with rapamycin and (or) paclitaxel. Cell proliferation was assessed by MTT assay. The interaction of rapamycin and paclitaxel was estimated by Jin Zhengjun's method. Cell apoptosis was detected by flow cytometry (FCM). The expression of survivin in A2780 and SKOV3 cells was detected by reverse transcription-polymerase chain reaction (RT-PCR).
When treated with rapamycin combined paclitaxel for 72 h, the proliferation inhibition rate was 34.9% for A2780 cells and 37.1% for SKOV3 cells, which was significantly higher than those of the cells treated with rapamycin or paclitaxel alone (P<0.01). These 2 drugs showed synergistic effect (q>1.15). The apoptosis of A2780 and SKOV3 cells were induced by rapamycin and paclitaxel; the apoptosis rate reached to the peak when the cells were treated with rapamycin combined paclitaxel. The expression of survivin in A2780 and SKOV3 cells was declined obviously after treatment of rapamycin combined paclitaxel.
Rapamycin and paclitaxel could inhibit proliferation and induce apoptosis of A2780 and SKOV3 cells in vitro, and down-regulate the expression of survivin. These 2 drugs have synergistic effect on cell proliferation.
既往研究证实，雷帕霉素靶蛋白（mTOR）在恶性肿瘤的发生发展中起重要作用。本研究旨在探讨mTOR的选择性抑制剂雷帕霉素联合紫杉醇对卵巢癌细胞株A2780和SKOV3凋亡的影响，并探讨其分子机制。
用雷帕霉素和（或）紫杉醇处理A2780和SKOV3细胞。采用MTT法评估细胞增殖。用金正军法评估雷帕霉素与紫杉醇的相互作用。采用流式细胞术（FCM）检测细胞凋亡。采用逆转录-聚合酶链反应（RT-PCR）检测A2780和SKOV3细胞中生存素的表达。
雷帕霉素联合紫杉醇处理72 h时，A2780细胞的增殖抑制率为34.9%，SKOV3细胞为37.1%，显著高于单独用雷帕霉素或紫杉醇处理的细胞（P<0.01）。这两种药物显示出协同作用（q>1.15）。雷帕霉素和紫杉醇诱导A2780和SKOV3细胞凋亡；雷帕霉素联合紫杉醇处理细胞时凋亡率达到峰值。雷帕霉素联合紫杉醇处理后，A2780和SKOV3细胞中生存素的表达明显下降。
雷帕霉素和紫杉醇在体外可抑制A2780和SKOV3细胞的增殖并诱导其凋亡，下调生存素的表达。这两种药物对细胞增殖有协同作用。
