Wang Zehua, Xie Yanhua, Wang Hongbo
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefong Dadoo, Wuhan, China.
Cancer Biol Ther. 2005 Jul;4(7):716-9. doi: 10.4161/cbt.4.7.1782. Epub 2005 Jul 2.
To investigate the role of antiapoptosis gene, survivin involved in regulating cell sensitivity to taxanes and platinum compounds.
Cultured human epithelial ovarian cancer cell line A2780 and its platinum(DDP)-resistance cell line A2780/DDP were divided into three groups as control, treatment with DDP, and treatment with Taxol Expression of mdr1 and survivin genes in each group was detected by using reverse transcription-polymerase chain reaction (RT-PCR). Apoptosis in the ovarian cancer cell lines was measured by flow cytometry.
After treatment with DDP for 48 h, relative survivin expression was significantly lower than that of no drug given (p<0.05). In A2780/DDP cells, expression of Survivn was obviously higher than that of the control group (P<0.05) after treatment of DDP for 48 h. Interestingly, survivin mRNA level was significantly decreased after treatment with Taxol for 48 h in the A2780/DDP-Taxol group compared with that in the control group. Apoptosis rate of A2780 cells was significantly increased to 46.21% and 44.46%, respectively, with treatment of DDP and Taxol. However, apoptosis rate in A2780/DDP was only 20.04% after DDP treatment for 48 h, demonstrating the presence of resistance to DDP in A2780/DDP cells.
This study demonstrated that changes in survivin mRNA level were related to the chemotherapy-induced apoptosis. Survivin may be considered as a biological indicator of the chemo-resistance of ovarian cancer.
探讨抗凋亡基因生存素（survivin）在调节细胞对紫杉烷类和铂类化合物敏感性中的作用。
将培养的人上皮性卵巢癌细胞系A2780及其铂（顺铂，DDP）耐药细胞系A2780/DDP分为三组，即对照组、DDP处理组和紫杉醇处理组。采用逆转录-聚合酶链反应（RT-PCR）检测各组中多药耐药基因1（mdr1）和生存素基因的表达。通过流式细胞术检测卵巢癌细胞系中的细胞凋亡情况。
DDP处理48小时后，生存素相对表达量显著低于未给药组（p<0.05）。在A2780/DDP细胞中，DDP处理48小时后，生存素表达明显高于对照组（P<0.05）。有趣的是，与对照组相比，A2780/DDP-紫杉醇组经紫杉醇处理48小时后，生存素mRNA水平显著降低。A2780细胞经DDP和紫杉醇处理后，凋亡率分别显著升高至46.21%和44.46%。然而，A2780/DDP细胞经DDP处理48小时后凋亡率仅为20.04%，表明A2780/DDP细胞对DDP存在耐药性。
本研究表明生存素mRNA水平的变化与化疗诱导的细胞凋亡有关。生存素可被视为卵巢癌化疗耐药的生物学指标。
