天津医药

天津医药 ›› 2020, Vol. 48 ›› Issue (3): 187-190.doi: 10.11958/20192856

• 实验研究 • 上一篇    下一篇

采用体内实验探讨 IL-17A促进卵巢癌腹腔种植瘤顺铂耐药的机制

陈燕，牛秀珑，郁春艳，李岩，邓为民   

  1. 1天津医科大学基础医学院免疫学系（邮编 300070）；2中国人民武装警察部队后勤学院附属医院感染性疾病科
  • 收稿日期:2019-09-17 修回日期:2019-12-17 出版日期:2020-03-15 发布日期:2020-04-11
  • 通讯作者: 邓为民 E-mail:dengweimin@tmu.edu.cn

The mechanisms of IL-17A promoting the cisplatin-based drug resistance of ovarian cancer in vivo

CHEN Yan,NIU Xiu-long,YU Chun-yan1,LI Yan1,DENG Wei-min   

  1. 1 Department of Immunology, Tianjin Medical University, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Diseases and Microenvironment of Ministry of Education of China, Tianjin 300070, China; 2 Department of Infectious Diseases, Hospital Affiliated to Logistics College of Chinese People’s Armed Police Forces
  • Received:2019-09-17 Revised:2019-12-17 Published:2020-03-15 Online:2020-04-11

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摘要： 目的 探讨 IL-17A促进卵巢癌（OVCA）腹腔种植瘤顺铂（DDP）耐药的体内机制。方法 以 C57BL/6遗传背景的野生型（WT）小鼠和 IL-17A-deficient（IL-17A-/-）小鼠，雌性，各 24 只为研究对象，随机分为 WT 对照组、IL-17A-/-对照组、WT治疗组、IL-17A-/-治疗组，每组 6只。腹腔注射相同基因背景来源的小鼠卵巢癌细胞系 ID8细胞，建立腹腔种植瘤动物模型。经 DDP或等量生理盐水给药 4周和 6周后，处死小鼠，打开腹腔观察并统计腹壁、大网膜、肠系膜及主要脏器表面瘤结节形成情况。采用免疫组化染色检测 WT小鼠和 IL-17A-/-小鼠对照组肿瘤组织中 IL-17A、ABCG2、MDR1及 Gli1表达情况，以探讨内源性 IL-17A促进卵巢癌 DDP耐药的分子机制。Western blot检测各组小鼠卵巢癌种植瘤组织中 ABCG2、MDR1 及 Gli1 的表达情况。结果 WT 对照组腹腔内瘤结节数明显高于 IL-17A-/-对照组，其治疗组腹腔内瘤结节数也高于 IL-17A-/-治疗组（P＜0.05）；WT对照组小鼠腹腔肿瘤组织中 ABCG2、MDR1、Gli1蛋白表达水平明显高于 IL-17A-/-对照组，同样地，WT治疗组小鼠腹腔肿瘤组织中 ABCG2、MDR1、Gli1蛋白表达水平也明显高于 IL-17A-/-治疗组（P＜0.05）。结论 内源性 IL-17A通过 Gli1介导的 Hh信号通路上调耐药相关蛋白 ABCG2和 MDR1的表达，进而促进卵巢癌腹腔种植瘤的DDP耐药。

关键词: 白细胞介素 17, 顺铂, 抗药性, 肿瘤, 卵巢肿瘤, 模型, 动物

Abstract: Objective To explore the in vivo mechanisms of IL-17A promoting the cisplatin-based drug resistance of ovarian cancer. Methods Wild type (WT) and IL-17A-defcient (IL-17A-/-) mice with C57BL/6 genetic background were used as research objects. Twenty-four female C57BL/6 WT mice and twenty-four female IL-17A-/- mice were randomly divided into WT control group, IL-17A-/- control group, WT treatment group and IL-17A-/- treatment group, with six mice in each group. The mouse ovarian cancer cell line ID8 cells with the same genetic background were intraperitoneally injected to establish the animal model of abdominal implantation of tumor. After four weeks and six weeks of administration with DDP or equivalent saline, the mice were sacrificed, and the formation of tumor nodules in the abdominal wall, omentum, mesentery and major organs were counted. The expressions of IL-17A, ABCG2, MDR1 and Gli1 were detected by the method of immunohistochemistry in WT and IL-17A-/- control group tissues to explore the mechanisms of endogenous IL-17A promoting the cisplatin-based drug resistance of ovarian cancer. Western blotting assay was used to detect the expressions of ABCG2, MDR1 and Gli1 in ovarian cancer tissues. Results The number of intraperitoneal nodules was significantly higher in the WT control group than that in the IL-17A-/- control group, and the number of intraperitoneal nodules was also higher in the WT treatment group than that in the IL-17A-/- treatment group（P＜0.05）. The expressions of ABCG2 MDR1 and Gli1 in abdominal tumor tissues were significantly higher in WT control group than those in IL-17A-/- control group. Similarly,these expression levels in abdominal tumor tissues were significantly higher in WT treatment group than those in IL-17A-/-treatment group（P＜0.05）. Conclusion Endogenous IL-17A can up-regulate the expressions of drug-resistant related proteins ABCG2 and MDR1 through the Hh signaling pathway mediated by Gli1, thereby promoting cisplatin-based drug resistance of OVCA.

Key words: interleukin-17, cisplatin, drug resistance, neoplasm, ovarian neoplasms, models, animal