阻断STAT3信号转导通路对人胰腺癌细胞生长的影响

Effect of blocking STAT3 signaling pathway on growth of human pancreatic cancer cells

目的:探讨Janus激酶(Janus kinase,JAK)特异性抑制剂AG490阻断STAT3信号转导通路对高表达STAT3的人胰腺癌细胞系SW1990生长增殖的作用及其机制。方法:使用AG490处理人胰腺癌细胞系SW1990,MTT法检测细胞增殖状态,流式细胞仪检测细胞凋亡,Western blot检测STAT3信号转导通路成员的表达。结果:AG490作用于人胰腺癌细胞系SW1990后,细胞增殖水平明显下降(P<0.05);细胞凋亡百分比显著升高(P<0.05);Western blot显示SW1990细胞中磷酸化STAT3(p-STAT3)、bcl-xL和cyclin D1蛋白表达明显降低(P<0.05)。结论:STAT3信号转导通路在胰腺癌进展过程中起着重要作用;阻断STAT3信号转导通路可抑制人胰腺癌细胞增殖,促进其凋亡;以STAT3信号转导通路为靶点的治疗策略可能为胰腺癌治疗提供新的思路。

Objective： To investigate the effect of blocking signal transducer and activator of transcription 3 （STAT3） signa ling pathway by Janus kinase （JAK） specific inhibitor AG490 on the growth and proliferation of SW1990 human pancreatic cancer cell line harboring constitutive active STAT3 and the underlying mechanism. Methods： AG490 was added into the culture media of SW1990 human pancreatic cancer cells. Cell viability was measured by MTT assay. （Tell apoptosis was detected by flow eytometry. The expression of the STAT3 signaling pathway components was determined hy Western blot. Results： The growth and proliferation of pancreatic cancer cells decreased significantly after AG490 treatment （P〈0.05） ; the percentage of apoptosis increased significantly（P〈0.05）. Western blot analysis showed that protein expression of phosphorylated STAT3 （pSTAT3）, bel-xL, and eyelin D1 in SW1990 pancreatic cancer cells decreased significantly. Conclusion ： STAT 3 signaling pathway plays an important role in the progression of pancreatic cancer. Blocking STAT 3 signal pathway inhibits the proliferation and promotes the apoptosis of pancreatic cancer cells. STAT 3 signaling pathway may provide a novel therapeutic target for the treatment of pancreatic cancer.