目的： 探究白介素22（interleukin-22，IL-22）对结直肠癌细胞增殖的影响，并阐明其信号通路机制。 方法： Real-time PCR检测结直肠癌细胞SW480和SW620中IL-22受体1（IL-22 receptor 1， IL-22R1 ）mRNA的表达；采用不同质量浓度IL-22(0、1、5、10 ng/ml) 处理结直肠癌细胞，MTT法及克隆形成实验检测IL-22对SW480和SW620细胞增殖的影响；IL-22处理SW480和SW620细胞不同时间后，采用Western blotting检测其STAT3、AKT、ERK、JNK、P38蛋白磷酸化的情况；观察特异性STAT3磷酸化抑制剂LLL12处理是否影响IL-22诱导的结直肠癌细胞的促增殖效应。 结果： IL-22R1 mRNA在结直肠癌SW480、SW620细胞中均有表达。IL-22剂量依赖性地促进SW480和SW620细胞增殖，10 ng/ml IL-22作用后，SW480与SW620细胞增殖倍数均明显增高\[（5.18±0.212） vs （2.64±0.27），（8.14±0.61） vs （6.08±0.096）；均P<001\]；且IL-22可提高SW480与SW620细胞克隆形成能力，细胞克隆数明显多于空白对照组\[（1 680.67±124.05） vs （730±64.29），(2 668±116.37） vs （1 294±171.61）；均P<0.01\]。Western blotting证实IL-22能显著活化STAT3通路，而对AKT、ERK、JNK、P-38通路影响不明显；STAT3抑制剂LLL12处理后，IL-22对SW480和SW620细胞的促增殖效应明显减弱。 结论： IL-22通过活化STAT3信号通路促进结直肠癌细胞SW480和SW620的增殖。

Objective:To explore the effect of IL-22 on the proliferation of colorectal cancer cells and to illustrate its underlying molecular mechanism. Methods: The relative expression levels of IL-22 receptor 1 ( IL-22R1 ) mRNA in colorectal cancer SW480 and SW620 cells were detected by real-time PCR. The different mass concentrations of IL-22 (0, 1, 5, 10 ng/ml) were used to treat colorectal cancer cells. The effect of IL-22 on the proliferation of SW480 and SW620 cells was analyzed by MTT assay and colony formation assay. SW480 and SW620 cells were stimulated with IL-22 for various time points and were subjected to Western blotting for the detection of protein phosphorylations, including STAT3, AKT, ERK, JNK and P38. Whether the specific inhibitor LLL12 blocking phosphorylation of STAT3 could promote the proliferation of colorectal cancer cells induced by IL-22 was observed. Results: IL-22R1 mRNA was expressed in colorectal cancer cells (SW480, SW620). IL-22 can promote the proliferation of SW480 and SW620 cells in a dose-dependent manner. After the treatment with IL-22 (10 ng/ml), the cell proliferation folds were significantly increased (SW480: \[5.18±0.212\] vs \[2.64±0.27\], SW620: \[814±0.61\] vs \[6.08±0.096\], P<0.01). Moreover, IL-22 enanced the colony formation ability of SW480 and SW620 cells. The colony numbers of IL-22 treating group were significantly higher compared with the control group (\[1 680.67±124.05\] vs \[730±64.29\], \[2 668±116.37\] vs \[1 294±171.61\], P<0.01). Western blotting demonstrated that STAT3 pathway can be activated after the treatment of IL-22. However, there was no significant alteration in AKT, ERK, JNK, P38 pathways. The proliferative effect of IL-22 can be attenuated after the treatment of STAT3 phosphorylation inhibitor LLL12. Conclusion: IL-22 may promote the proliferation of colon cancer SW480 and SW620 cells via STAT3 signaling pathway.

上海市科委基础研究重大项目（No.10DJ1400504）；上海交通大学医工交叉研究基金项目（No.YG2011MS32）