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.
Methods: 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).
Results: 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.
Conclusions: 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.