title: Autophagy impacts on oxaliplatin-induced hepatocarcinoma apoptosis via the IL-17/IL-17R-JAK2/STAT3 signaling pathway.
abstract: The interleukin (IL)-17/IL-17 receptor (IL-17R) complex has been shown to be important for the regulation of inflammation; however, its role in the regulation of tumor processes has recently emerged as a research focus. The present study demonstrated that oxaliplatin was able to increase the levels of IL-17/IL-17R in hepatocellular carcinoma (HCC) patients and cells lines, and that it had important roles in reducing the susceptibility of the cells to oxaliplatin-induced apoptosis. Furthermore, the expression of autophagy-related proteins was induced by IL-17/IL-17R and autophagy was shown to induce resistance to oxaliplatin in HCC. In addition, the janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway was shown to be an important pathway in the induction of autophagy in response to oxaliplatin. Autopjhagy was inhibited by 3-methyladenine and JAK2/STAT3 signaling was blocked by AG490, which induced apoptosis in SMMC7721 cells treated with oxaliplatin. The results of the present study may help to elucidate the mechanism underlying the role of IL-17/IL-17R-induced autophagy in the chemoresistance of HCC, as well as help to establish and develop measures to overcome chemoresistance in HCC.
authors.affiliation: Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300000, P.R. China; Clinical Laboratory, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Wu
authors.affiliation: Clinical Laboratory, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China.
authors.forename: Jiapei
authors.initials: J
authors.lastname: Guo
authors.affiliation: Clinical Laboratory, Hebei Medical University Second Hospital, Shijiazhuang, Hebei 050000, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Clinical Laboratory, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Clinical Laboratory, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China.
authors.forename: Junmao
authors.initials: J
authors.lastname: Chen
authors.affiliation: Clinical Laboratory, Tangshan Fengrun Region Second People's Hospital, Tangshan, Hebei 063000, P.R. China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300000, P.R. China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Yuan
keywords: autophagy; hepatocellular carcinoma; interleukin-17/interleukin-17 receptor; janus kinase 2/signal transducer and activator of transcription 3