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Research Papers:

IL-17A exacerbates cisplatin-based resistance of OVCA via upregulating the expression of ABCG2 and MDR1 through Gli1-mediated Hh signaling

Xiulong Niu, Wenxing Liu, Yue Wang, Xiaomei Liu, Hongjian Zhang, Zhijun Li, Hongzhao Li, Yoichiro Iwakura and Weimin Deng _

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Abstract

Xiulong Niu1,2,*, Wenxing Liu1,*, Yue Wang3, Xiaomei Liu4, Hongjian Zhang1, Zhijun Li1, Hongzhao Li1, Yoichiro Iwakura5, Weimin Deng1

1Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Diseases and Microenvironment of Ministry of Education of China, Tianjin Medical University, Tianjin 300070, China

2Department of Infectious Diseases, Hospital Affiliated to Logistics College of Chinese People’s Armed Police Forces, Tianjin 300162, China

3Department of Immunology, Logistics College of Chinese People’s Armed Police Forces, Tianjin 300162, China

4Department of Obstetrics and Gynecology, Tianjin Medical University General Hospital, Tianjin 300052, China

5University Research Administration Center, Tokyo University of Science, Tokyo125-8585, Japan

*These authors have contributed equally to this work

Correspondence to:

Weimin Deng, e-mail: [email protected]

Keywords: IL-17A, cisplatin, drug-resistance, ovarian cancer, sensitivity

Received: October 08, 2015     Accepted: May 04, 2016     Published: July 18, 2016

ABSTRACT

The major obstacle of the tumor chemotherapy, including ovarian cancer (OVCA), is drug resistance. However, the relevance of IL-17A with drug-resistance of OVCA has been poorly elaborated. In this study, we used 2 human OVCA cell lines to investigate the effects of IL-17A on cisplatin (CDDP or DDP)-based resistance in OVCA cells and the underlying mechanisms. Meanwhile, IL-17A-deficient mice and ID8 were used to verify the IL-17A’s effects on OVCA chemo-resistance in vivo. Moreover, the relationship between IL-17A level and relevant indices were primarily assessed in ovarian specimens from 55 patients with OVCA. We found that rhIL-17A exacerbated DDP-based resistance of OVCA cells via up-regulating the expression of ABCG2 and MDR1 through Gli1-mediated Hh signal pathway. Animal experiment demonstrated that IL-17A significantly recede DDP-based treatment for ID8 tumor. Similar results were observed in preliminary clinical investigation. Our findings suggest that inhibiting IL-17A/IL-17RA-Gli1 signal may improve the resistance of OVCA to DDP.


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