IL-37 mediates the antitumor activity in renal cell carcinoma

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.

Medical oncology (Northwood, London, England). 2015 Oct 13 [Epub]

Yazhuo Jiang, Yili Wang, Liang Liang, Yang Gao, Juan Chen, Yi Sun, Yongyi Cheng, Yonggang Xu

Department of Urology, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, 710068, Shaanxi Province, China. , 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. Department of Urology, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, 710068, Shaanxi Province, China. , Department of Urology, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, 710068, Shaanxi Province, China. , Department of Urology, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, 710068, Shaanxi Province, China. , Department of Urology, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, 710068, Shaanxi Province, China. , Department of Urology, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, 710068, Shaanxi Province, China. , Department of Urology, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, 710068, Shaanxi Province, China.

PubMed