title: IL-37 mediates the antitumor activity in renal cell carcinoma.
abstract: Interleukin (IL)-37 is a natural suppressor of innate inflammatory and immune responses. IL-37 plays an important role in renal function and antitumor activity. The aim of this study was to investigate the role of IL-37 in renal cell carcinoma (Rcc). Serum IL-37 levels in 120 Rcc patients and 50 healthy controls were measured by enzyme-linked immunosorbent assay (ELISA). The Rcc cell lines A498 and Caki-1 were cultured with 0-100 ng/mL of recombinant human IL-37 protein (rhIL-37). Cancer cells were transfected with or without pcDNA3.1-IL-6 to alter IL-6 expression. Cell migration, proliferation, and apoptosis were tested by wound-healing assay, MTT, and flow cytometry, respectively. Levels of IL-6, pSTAT3 Y705, Bcl-2, cyclin D1, and HIF-1α were detected by qRT-PCR, ELISA, or western blot. Additionally, therapeutic effect of rhIL-37 was also confirmed in SCID mice. The expression of IL-37 was decreased in Rcc patients and was negatively correlated with tumor progression. In vitro, IL-37 markedly inhibited the migration and proliferation, and promoted apoptosis in Rcc cells. Furthermore, the expressions of IL-6, pSTAT3 Y705, HIF-1α, Bcl-2, and cyclin D1 were decreased by IL-37. However, these effects were reversed by the transfection of pcDNA3.1-IL-6. In vivo, tumor growth and gene expressions of IL-6 and HIF-1α were suppressed by IL-37. In conclusion, IL-37 might serve as a novel tumor suppressor in Rcc and exert its antitumor activity through inhibiting IL-6/STAT3 signaling.
authors.affiliation: Department of Urology, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, 710068, Shaanxi Province, China.
authors.forename: Yazhuo
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Institute for Cancer Research, School of Basic Medical Science, Health Science Center of Xi'an Jiaotong University, 76 Yanta XiLu, Xi'an, 710061, Shaanxi Province, China. yiliwangs@163.com.
authors.forename: Yili
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Urology, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, 710068, Shaanxi Province, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Urology, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, 710068, Shaanxi Province, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Urology, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, 710068, Shaanxi Province, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Urology, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, 710068, Shaanxi Province, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Urology, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, 710068, Shaanxi Province, China.
authors.forename: Yongyi
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Urology, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, 710068, Shaanxi Province, China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000188:drug therapy; D045744:Cell Line, Tumor; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D007375:Interleukin-1 / Q000097:blood* / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000097:blood* / Q000188:drug therapy; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011446:Prospective Studies; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; C508587:IL37 protein, human; D007375:Interleukin-1
keywords: Antitumor; IL-37; IL-6/STAT3 signaling; Renal cell carcinoma