JAK-STAT信号通路与人直肠癌发生发展的关系

Correlation between JAK-STAT signal pathway and the development of human rectal cancer

目的:探究正常直肠组织和直肠癌组织中JAK-STAT信号通路重要成员以及通路下游重要蛋白的表达变化情况及其临床意义,并通过体外实验观察STAT3对直肠癌细胞侵袭、转移以及增殖的影响。方法:收集2013年5月1日至2014年5月1日在本院行手术切除并经病理证实为直肠癌患者的癌组织和非直肠癌(痔疮、肛瘘肛裂、结肠炎、肠息肉等)患者正常直肠组织各50份,采用Western blotting法检测组织中STAT3、p-STAT3及JAK-STAT信号通路下游Cyclin D1、Bcl2的表达,分析STAT3蛋白表达与直肠癌临床病理特征关系。以慢病毒介导的STAT3-shRNA转染直肠癌细胞Colo320,采用MTT法和Transwell侵袭和迁移实验检测sh-RNA干扰STAT3表达对直肠癌Colo32细胞增殖、侵袭和转移的影响。结果:与正常组织相比,直肠癌组织中STAT3蛋白的表达显著升高(P<0.01),p-STAT3、Cyclin D1和Bcl2蛋白的表达也明显高于正常直肠组织(P<0.05);STAT3蛋白表达水平与直肠癌分化程度、淋巴转移有关(P<0.05),而与肿瘤大小无关(P>0.05)。慢病毒介导的shRNA转染Colo320细胞可有效抑制其STAT3和p-STAT3表达,沉默STAT3后Colo320细胞的增殖和侵袭转移能力显著下降(P<0.05)。结论:STAT3能通过影响JAK-STAT信号通路下游重要蛋白的表达,促进直肠癌的增殖、侵袭和转移,研究结果为直肠癌的防治提供潜在的新靶点。

Objective: To study the possible role for the JAK-STAT signaling pathway in the pathogenesis of rectal cancer. Methods: Cancerous and non-cancerous( control) tissue specimens were collected at surgical resection from 50 rectal cancer patients and 50 non-rectal cancer patients,respectively,who were admitted to our hospital between May,2013 and May,2014. Levels of STAT3,p-STAT3 and the two major protein molecules,cyclin D1 and Bcl2,downstream of the JAK-STAT signal pathway in these clinical specimens were assessed by Western blotting analysis and were analyzed statistically for their correlations with the clinical pathological features of the patients. To further evaluate the influence of STAT3 on rectal cancer cell growth,the proliferative activity and invasion ability of colonic carcinoma Colo320 cells after siRNA-mediated silencing of the STAT3 gene was assessed by MTT Transwell migration assays,respectively. Results:Levels of STAT3 were significantly higher in rectal cancer specimens than in non-cancerous control specimens( P <0. 01),so were levels of p-STAT3,cyclin D1 and Bcl2( P < 0. 05). STAT3 protein levels in cancerous specimens were significantly correlated with the differentiation degree and lymphatic metastasis of rectal cancer( P < 0. 05),but not with the tumor size( P > 0. 05). STAT3 silencing resulted in significant decreases in Colo320 cell proliferation,invasion and metastasis( P < 0. 05). Conclusion: STAT3 is involved in the proliferation,invasion and metastasis of colorectal cancer through a JAK-STAT signaling-dependent mechanism and thus may serve as a potential therapeutic target for colorectal cancer.