[Induction effect of rapamycin combined paclitaxel on apoptosis of ovarian cancer cell lines A2780 and SKOV3 and the molecular mechanism].
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.
Ma
Xiang-Yi
XY
Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
Wang
Shi-Xuan
SX
Liu
Yan
Y
Liu
Rong-Hua
RH
Lu
Yun-Ping
YP
Ma
Ding
D
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D004357:Drug Synergism; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020123:Sirolimus / Q000494:pharmacology*; D000077022:Survivin
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D000077022:Survivin; D017239:Paclitaxel; D020123:Sirolimus