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