title: Interleukin-22 suppresses the growth of A498 renal cell carcinoma cells via regulation of STAT1 pathway.
abstract: BACKGROUND
  Renal cell carcinoma (RCC) is one of the most common kidney cancers and is highly resistant to chemotherapy. Accumulating evidence suggests that interleukin-22 (IL-22) may mediate host defense against varietal pathogens as a proinflammatory and anti-inflammatory cytokine. The purpose of this study is to assess the inhibitory effects of IL-22 on human RCC cell line A498 and to investigate the possible mechanisms underlying the anti-tumor effects of this cytokine.
  
  
  METHODS
  A498 cells, a RCC cell line, were used to assess the inhibitory growth effects of IL-22 using the MTT assay and flow cytometric analysis in vitro. BALB/C nude mice bearing A498 cell xenografts were used to examine the antitumor efficacy of IL-22 in vivo. Western blotting assay was performed to detect the regulation of the intracellular signaling pathway of IL-22.
  
  
  RESULTS
  We found that IL-22 suppressed the growth of A498 cells in a dose-dependent manner and inhibited the growth of A498 xenografts. We also observed that IL-22 produced a dose-dependent inhibitory effect on A498 cells that involved the induction of G2/M cell cycle arrest without cell apoptosis. Moreover, we showed that the phosphorylation of STAT1 was increased and the phosphorylation of ERK1/2 was attenuated in A498 cells exposed to IL-22. The growth inhibition of A498 cells was partially revised after IL-22 treatment as the expression of STAT1 was knocked down. And inflammatory cytokines, interferon-α and tumor necrosis factor-α (TNF-α) were barely involved in the suppression of A498 cell xenografts treated with IL-22.
  
  
  CONCLUSIONS
  IL-22 dose-dependently suppresses RCC cell line A498 cells in vitro and induces growth inhibition of A498 cell-bearing mouse xenografts. These results suggest that the anti-RCC effects of IL-22 are at least partially mediated through regulation of STAT1 signaling pathways and G2/M cell cycle arrest, rather than by inducing apoptosis and inflammatory cytokines.
authors.affiliation: Department of Urology Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China. Fengbo_zhang@hotmail.com
authors.forename: Fengbo
authors.initials: F
authors.lastname: Zhang
authors.forename: Donghao
authors.initials: D
authors.lastname: Shang
authors.forename: Yuhai
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007378:Interleukins / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050794:STAT1 Transcription Factor / Q000502:physiology*; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D050794:STAT1 Transcription Factor; D000097043:Interleukin-22; C494079:STAT1 protein, human