IL-17A促进卵巢癌顺铂耐药的体外机制探讨

目的:探究IL-17A促进卵巢癌顺铂（DDP）耐药的体外机制。方法:应用流式细胞术分析外源性rhIL-17A对DDP诱导的A2780（顺铂敏感卵巢癌细胞株）和OVCAR3（顺铂耐药卵巢癌细胞株）细胞的凋亡和周期分布变化的影响，并以IL-17RAmAb进行相应的阻断实验。结果:rhIL-17A对A2780和OVCAR3细胞的凋亡无显著影响；但可显著降低DDP对A2780和OVCAR3细胞的毒性作用（P<0.05），以IL-17RAmAb进行阻断实验可部分消除rhIL-17A对DDP诱导的A2780和OVCAR3细胞凋亡的阻滞作用（P<0.05）。rhIL-17A对A2780和OVCAR3细胞的周期分布无显著影响；但可显著抑制 DDP诱导的A2780和OVCAR3细胞周期阻滞（P <0.05），使A2780和OVCAR3细胞的G0/G1期比例增加，G2+S期比例减少。结论: IL-17A可通过IL-17RA抑制DDP诱导的卵巢癌细胞凋亡，同时可抑制DDP诱导的卵巢癌细胞周期阻滞，从而加剧以DDP为基础的卵巢癌化疗耐药性。

Study on the underlying mechanisms of IL-17A promoting the cisplatin-based resistance of ovarian cancer

Objective: To explore the underlying mechanisms of IL-17A promoting the cisplatin-based resistance of ovarian cancer. Methods: Flow cytometry assay was used to detect the effect of exogenous rhIL-17A on the cisplatin-based cell apoptosis and cycle distribution of A2780 and OVCAR3 cells, and then neutralizing IL-17RAmAb was applied to perform the blocking test. Results: RhIL-17A alone had no effect on the apoptosis of A2780 and OVCAR3 cells, but it could significantly inhibit the cytotoxicity of DDP to A2780 and OVCAR3 cells (P <0.05). Furthermore, neutralizing IL-17RAmAb could markedly block the above effect of rhIL-17A on DDP-sensitivity (P <0.05). There was no effect of rhIL-17A on cell cycle distribution of A2780 and OVCAR3 cells. After pre- treatment with rhIL-17A, the DDP effect on cell cycle might be changed partially by increasing the G0/G1 phase and decreasing the G2+S phase (P <0.05). Conclusion: IL-17A could inhibit the cisplatin-based cell apoptosis of ovarian cancer cell, partially through IL-17RA signal pathway. Moreover, IL-17A could also repress the effects of DDP on cell cycle distribution of ovarian cancer cell, which may provide a novel strategy to improve the chemoresistance of ovarian cancer.