title: IL-33-induced JNK pathway activation confers gastric cancer chemotherapy resistance.
abstract: Inflammation is regarded as one of the major hallmarks of tumors, and has a very close relationship with gastric cancer. Interleukin-33 (IL-33), a new member of the IL-1 family, plays an important role in both inflammatory disease and tumors. The present study was designed to explore the effects of IL-33 on the proliferation, drug sensitivity, and the invasiveness of gastric cancer cells in vitro. IL-33 at concentrations lower than 100 pg/ml did not alter the inhibitory rate of gastric cancer cells. Moreover, IL-33 at these low concentrations protected against platinum-induced apoptosis in various gastric cancer cell lines, yet not in normal gastric epithelial cells. We also found that IL-33 increased the activation of the JNK pathway, and enhanced the expression of ST2. Furthermore, SP600125, a selective inhibitor of the JNK pathway, significantly blocked the protective effects of IL-33 in gastric cancer cells. In addition, Matrigel invasion assay showed that IL-33 markedly promoted gastric cancer cell invasion. In conclusion, the present study demonstrated that IL-33 protected against platinum-induced apoptosis and promoted cell invasion via activation of the JNK pathway in gastric cancer cells. In light of the prevalence of platinum-based chemotherapeutics in the treatment of gastric cancer, our results suggest that the level of IL-33 should be monitored during the treatment of gastric cancer, particularly when using platinum-based chemotherapeutics.
authors.affiliation: Cancer Institute, Yinzhou People's Hospital, Ningbo, Zhejiang 315020, P.R. China.
authors.forename: Xiao-Lei
authors.initials: XL
authors.lastname: Ye
authors.affiliation: Cancer Institute, Yinzhou People's Hospital, Ningbo, Zhejiang 315020, P.R. China.
authors.forename: Ya-Rong
authors.initials: YR
authors.lastname: Zhao
authors.affiliation: Cancer Institute, Yinzhou People's Hospital, Ningbo, Zhejiang 315020, P.R. China.
authors.forename: Guo-Bin
authors.initials: GB
authors.lastname: Weng
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Cancer Institute, Yinzhou People's Hospital, Ningbo, Zhejiang 315020, P.R. China.
authors.forename: Xue-Ni
authors.initials: XN
authors.lastname: Wei
authors.affiliation: Division of Drugs and Pharmacology, Ningbo Institute of Medical Sciences, Ningbo, Zhejiang 315020, P.R. China.
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Shao
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ji
mesh_terms: D000873:Anthracenes / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000067596:Interleukin-33 / Q000008:administration & dosage / Q000235:genetics*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology
chemical_list: D000873:Anthracenes; D000067596:Interleukin-33; C432165:pyrazolanthrone