p-STAT3与E-cadherin在胰腺癌中的表达及其临床意义

Expression of p-STAT3 and E-cadherin in pancreatic cancer and their clinical significances

目的:观察信号传导和转录激活因子3 (STAT3)活化形式-磷酸化STAT3(p-STAT3)和上皮型-钙黏附素(E-cadherin)在胰腺癌组织及细胞中的表达及其临床意义,探讨STAT3信号通路在胰腺癌侵袭转移中的作用．方法:免疫组化检测34例胰腺癌和10例正常胰腺组织中p-STAT3和E-cad的表达,并分析其与胰腺癌临床病理特征的关系．细胞侵袭测定试剂盒检测胰腺癌细胞株SW1990和CaPan-2侵袭能力:分别采用Western blot和电泳迁移率变迁实验(EMSA)检测2种细胞中p-STAT3蛋白表达及STAT3-DNA结合活性．结果:免疫组化发现p-STAT3在胰腺癌组织中存在高表达(64．7%),与临床分期及淋巴结转移有关(P=0．017,P=0．013);E-cad在胰腺癌组织中表达明显降低,与组织学分级(P= 0．002)、临床分期(P=0．034)及淋巴结转移(P=0．019)有关．在胰腺癌组织中,p-STAT3与E-cad的表达呈负相关(r=-0．537,P=0．001)．体外侵袭实验发现SW1990细胞比CaPan-2细胞具有更高的侵袭能力(P＜0．05)．Western blot发现在胰腺癌高侵袭力细胞株SW1990中p-STAT3蛋白呈高表达,而在低侵袭力细胞株CaPan-2中呈低表达;EMSA实验亦证实SW1990细胞较CaPan-2细胞具有更高的STAT3-DNA结合活性(P＜0．05)．结论:p-STAT3与胰腺癌侵袭转移及E-cad异常表达密切相关;联合检测两种蛋白对于胰腺癌恶性潜能的判断具有一定的参考价值．

AiM： To investigate the expression of phosphorylated signal transduction and activators of transcription-3 （p-STAT3） and E-cadherin as well as their correlations with the clinicopathological parameters in pancreatic cancer, and to reveal the role of STAT3 signal pathway in the invasion and metastasis of pancreatic cancer. METHODS： Immunohistochemistry was used to detect the expression of p-STAT3 and E-cadherin in 34 cases of pancreatic cancer and 10 cases of normal pancreatic tissues. Cell invasion assay kit was used to examine the invasion ability of pancreatic cancer cells SW1990 and CaPan-2. Western blot and electrophoretic mobility shift assay （EMSA） were applied to detect the protein expression of p-STAT3 and STAT3 DNA-binding activity in SW1990 and CaPan-2 cells.RESULTS： Immunohistochemistry revealed high expression of p-STAT3 （64.7%） but low expression of E-cadherin in pancreatic cancer. The expression of p-STAT3 was significantly correlated with the clinical stages （P= 0.017） and lymph node metastasis （P = 0.013）, and the expression of E-cadherin was correlated with the pathological degrees （P= 0.002）, clinical stages （P = 0.034） and lymph node metastasis （P = 0.019）. There was a negative correlation between p-STAT3 and E-cadherin expression in pancreatic cancer （r= -0.537, P = 0.001）. Cell invasion assay indicated a more invasive ability in SW1990 cells than that in CaPan-2 cells （P 〈 0.05）. Finally, Western blot and EMSA showed that p-STAT3 protein level and STAT3 DNA-binding activity were significantly higher in SW1990 cells as compared with those in CaPan-2 cells （P 〈 0.05）. CONCLUSION： The expression of p-STAT3 is closely related to the invasion and metastasis of pancreatic cancer and abnormal expression of E-cadherin. The combined detection for these two proteins may be useful in determining of the metastasis potency of pancreatic cancer.