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目的探讨Janus激酶特异性抑制剂JSI-124阻断信号转导与转录激活因子3(STAT 3)信号通路对人胆囊癌细胞生长的作用及其机制。方法体外培养人胆囊癌细胞株GBC,分为对照组(A组)和JSI-124 250、500、1000nmol/L不同浓度组(分别为B1、B2、B3组)。采用MTT法检测细胞增殖,流式细胞术检测细胞周期和细胞凋亡,Western blot法检测STAT3及其相关蛋白的表达。结果与A组相比,JSI-124呈时间和浓度依赖性地抑制GBC细胞增殖,增加G2/M期细胞的比例,降低G0/G1期细胞的比例,增加细胞凋亡率,下调磷酸化STAT3(p-STAT3)、生存素、细胞周期素D1(cyclin D1)和B淋巴细胞瘤-白血病2(Bcl-2)蛋白表达(P<0.05或P<0.01)。结论 JSI-124通过下调p-STAT3、cyclin D1、Bcl-2和生存素的表达抑制人胆囊癌细胞增殖,促进细胞凋亡。以STAT3信号转导通路为靶点的治疗策略可能为胆囊癌治疗提供新的思路。
Objective To investigate the effect and mechanism of Janus kinase-specific inhibitor JSI-124 blocking the signal transduction and activator of transcription 3 (STAT3) signaling pathway on the growth of human gallbladder carcinoma cells. Methods Human gallbladder carcinoma cell line GBC was cultured in vitro. The cells were divided into control group (group A) and JSI-124 250,500,1000 nmol / L different concentration groups (B1, B2 and B3 respectively). Cell proliferation was detected by MTT assay. Cell cycle and apoptosis were detected by flow cytometry. Western blot was used to detect the expression of STAT3 and its related proteins. Results Compared with group A, JSI-124 inhibited the proliferation of GBC cells in a time and concentration-dependent manner, increased the proportion of cells in G2 / M phase, decreased the proportion of cells in G0 / G1 phase, increased the apoptosis rate and down-regulated phosphorylated STAT3 (p-STAT3), survivin, cyclin D1 and Bcl-2 protein expression (P <0.05 or P <0.01). Conclusion JSI-124 can inhibit the proliferation of human gallbladder carcinoma cells and promote apoptosis by down-regulating the expressions of p-STAT3, cyclin D1, Bcl-2 and survivin. The treatment strategy targeting STAT3 signal transduction pathway may provide a new idea for the treatment of gallbladder cancer.