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. METHODOLOGY: 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. PRINCIPAL FINDINGS: 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.
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Authors | Fengbo Zhang, Donghao Shang, Yuhai Zhang, Ye Tian |
Journal | PloS one
(PLoS One)
Vol. 6
Issue 5
Pg. e20382
( 2011)
ISSN: 1932-6203 [Electronic] United States |
PMID | 21625390
(Publication Type: Journal Article)
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Chemical References |
- Interleukins
- STAT1 Transcription Factor
- STAT1 protein, human
- interleukin-22
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Topics |
- Animals
- Blotting, Western
- Cell Division
(drug effects, physiology)
- Cell Line, Tumor
- Dose-Response Relationship, Drug
- Humans
- Interleukins
(pharmacology, physiology)
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- STAT1 Transcription Factor
(physiology)
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