摘要
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。
Objective： To explore the underlying meehanisnls of IL-17A promoting the eisplatin-based resistance of ovarian cancer. Methods： Flow eytometry assay was used to detect the etteet of exogenous rhlL-17A on the eisplatin-based cell apoptosis and cycle distribution of A2780 and OVCAR3 cells, and then neutralizing IL-17RAmAb was applied to pertorm the blocking test. Results： RhlL- 17A alone had no etteet on the apoptosis of A2780 and OVCAR3 cells, but it could significantly inhibit the eytotoxieiU of DDP to A2780 and OVCAR3 cells （P〈0.05）. Furthemlore, neutralizing IL-17RAmAb could markedly block the above etteet of rhIL-17A on DDP- sensitivity （P 〈0.05）. There was no etteet of rhlL-17A on cell cycle distribution of A2780 and OVCAR3 cells. After pre- treatment with rhlL-17A, the DDP etteet on cell cycle might be changed partially by increasing the C0/C1 phase and decreasing the C2＋S phase （P 〈0.05）. Conclusion： IL-17A could inhibit the eisplatin-based cell apoptosis of ovarian cancer cell, partially through IL-17RA signal pathway. Moreover, IL-17A could also repress the etteets of DDP on cell cycle distribution of ovarian cancer cell, which may provide a novel strategy to improve the ehemoresistanee of ovarian cancer.
作者
徐灵灵
牛秀珑
张宏健
李稚君
陈燕
邓为民
XU Ling-ling;NIU Xiu-long;ZHANG Hong-jian;LI Zhi-jun;CHEN Yan;DENG Wei-min(Department of Immunology, Tianjin Medical University, Tianjin 300070, China;Department of Infectious Diseases, Hospital Affiliated to Logistics College of Chinese People＇s Armed Police Forces, Tianjin 300162, China;Department of Blood Transfusion, General Hospital, Tianjin Medical University, Tianjin 300052, China;Department of Orthopedics, General Hospital, Tianjin Medical University, Tianjin 300052, China)
出处
《天津医科大学学报》
2018年第3期192-196,共5页
Journal of Tianjin Medical University
基金
天津市教委重点项目(2016YD01)
天津市科委应用基础研究项目(15JCYBJC26000)
武警后勤学院博士启动金项目资助(WHB201610)
关键词
卵巢癌
IL-17A
顺铂
耐药
ovarian cancer
IL-17A
cisplatin
drug-resistance
