42℃温热联合顺铂对人卵巢癌细胞SKOV3毒性的影响

Enhanced cytotoxicity of cisplatin to human ovarian cancer SKOV-3 cells by 42℃ hyperthermia

目的探讨42℃温热联合化疗药物顺铂对人卵巢癌细胞株SKOV-3作用的规律及其机制。方法应用四氮唑蓝快速比色法测定42℃热疗组、单纯化疗组以及以不同序贯方式结合的热化疗组对人卵巢癌细胞SKOV-3的生长抑制率;流式细胞仪测定各组细胞周期的变化;金氏公式分析相互作用指数,评价温热化疗两因素联合的作用。结果 42℃单纯热疗和单纯化疗均对卵巢癌癌细胞有抑制和杀伤作用;42℃热疗与化疗药物以不同方式联合,抑制作用均强于单纯化疗组和单纯热疗组(P<0.05),尤以热化疗同时作用组效果最佳(P<0.001);细胞周期分析发现:42℃热疗降低了S期细胞所占比例;与单纯化疗组相比,先化疗后热疗组、先热疗后化疗组和热化疗同时组的S期细胞所占比例减少,G1期细胞增多,其中热化疗同时组增减的幅度最大。结论 42℃温热可以明显增强化疗药顺铂的毒性,结合方式上以热化疗同时进行最佳,其作用机制可能与干扰细胞周期有关。

[Objective] To investigate the function and mechanism of 42℃ hyperthermia and cisplatin on human ovarian cancer SKOV-3 cells in vitro. [ Method ] Tetrazolium-based colorimetric assay was used to measure growth inhibition rate of human ovarian cancer cells under different conditions, including 42℃ hyperthermia, simple chemotherapy and hyperthermia combined chemotherapy in different sequential modes. Flow cytometry was used to measure the change of cells cycles. The interaction index was also analyzed using jin＇s formula and the inhibition ef- fect of 42℃ hyperthermia combined with chemotherapy on human ovarian cancer cells was estimated. [Results] 42℃ hyperthermia and single drug had inhibition and killing effect on human ovarian cancer cells （SKOV-3） indi- vidually. When 42℃ hyperthermia combined with drug chemotherapy in different sequential modes, the inhibition effect was stronger than hyperthermia or chemotherapy separately （P 〈0.001）. Especially, the inhibition effect was most obvious when using hyperthermia and chemotherapy at the same time （P 〈0.001）. Flow cytometry showed that： 42℃ hyperthermia resulted in progressive decrease on cells in S phase; Compared with the group of single chemotherapy, the proportions of S phase cells of all groups of hyperthermia following chemotherapy, chemotherapy following hyperthermia and simultaneous treatment with hypertherrnia and chemotherapy decreased obviously, while the proportions of G phase cells increased. Among all these groups, changed range of simultaneous treatment group was the widest. [Conclusion] 42℃ hyperthermia can obviously enhance the cytotoxicity of DDP; The most effective way is hyperthermia combined with chemotherapy simultaneously; the anti-tumor mechanism may be related to dis- turbance of cell cycle.