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KMID : 1004820110120040181
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Journal of Biomedical Research
2011 Volume.12 No. 4 p.181 ~ p.193
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Growth Inhibition of Colon Cancer through Inactivation of STAT3 Pathway by IL-10 and IL-1ra Released from Murine Macrophage
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Won Do-Hee
Park Mi-Hee
Kown Sun-Mi
Jo Mi-Ran
Nam Sang-Yoon
Lee Beom-Jun
Yun Young-Won
Oh Ki-Wan
Han Sang-Bae
Hong Jin-Tae
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Abstract
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The objective of this study was to determine the effect of macrophages on growth of human colon cancer cells. The results showed that co-culture of colon cancer cells with macrophages inhibited the growth of colon cancer cells (HCT116 and SW620) depending on the number of macrophages, RAW 264.7 cells, and activated THP-1 cells accompanied by down regulation of pSTAT3 in cancer cells. We also found that expression and release of cancer cell growth inhibitory cytokines, IL-1 receptor antagonist (IL-1ra) and IL-10, was increased in macrophages. Blocking of the STAT3 pathway with specific inhibitor and siRNA of STAT3 abolished the growth of colon cancer cells and expression of IL-1ra and IL-10. In addition, neutralization of IL-1ra and IL-10 with antibodies resulted in reversal of macrophage-induced inhibition of cancer cell growth. These data showed that IL-1ra and IL-10 released from macrophages inhibit growth of colon cancer cells through inhibition of the STAT3 pathway.
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KEYWORD
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Macrophage, Colon cancer cells, IL-1ra, IL-10, STAT3
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