同时稳定抑制X连锁凋亡抑制蛋白和生存素表达对胰腺癌细胞上皮-间质转化及侵袭性的影响

Simultaneous inhibition of XIAP and survivin expression on EMT and invasion of human pancreatic cancer cells

目的:探讨同时抑制X连锁凋亡抑制蛋白(XIAP)和生存素(survivin)后,对胰腺癌Panc-1细胞上皮-间质转化(EMT)及侵袭性的影响,并初步探讨其机制。方法:在前期实验构建的胰腺癌Panc-1-XS细胞(XIAP和survivin同时稳定抑制)中,运用Transwell小室实验及划痕实验分别检测细胞侵袭和迁移能力;半定量Western印迹分别检测钙黏蛋白-E(E-cadherin,上皮标志物)、锌指转录因子(Slug)蛋白(间质标志物)及第10号染色体同源丢失性磷酸酶——张力蛋白基因(PTEN)和磷酸化蛋白激酶B(P-Akt)蛋白的表达情况。结果:Panc-1-XS细胞侵袭和迁移能力显著下降,同时伴随E-cadherin蛋白表达显著上调及Slug蛋白显著下调,即出现间质-上皮转化(MET);PTEN蛋白表达上调、P-Akt蛋白表达下调。结论:同时抑制XIAP和survivin表达,能部分逆转胰腺癌Panc-1细胞EMT表型,显著减弱其侵袭和迁移能力;此调控过程可能通过PTEN/PI3K/Akt途径实现。

To investigate the simultaneous inhibition of X-linked inhibitor of apoptosis protein （XIAP） and survivin expression on epithelial-mesenchymal transition （EMT） and invasiion of pancreatic cancer cells Panc-1, and its mechanism. Methods： On the established human pancreatic cancer cells Panc-l-XS, the expression of XIAP and survivin was inhibited simultaneously. Cell invasion and migration were detected by Transwell chamber experiments and scratch test, and the expression of epithelial marker E-cadherin, mesenchymal markers Slug, phosphatase and tensin homolog deleted on chromosome ten （PTEN） and P-Akt protein was determined by Western blot. Results： Cell invasion and migration of Panc-l-XS cells decreased significantly, accompanied by significantly upregulated protein expression of E-cadherin, and significantly declined proteinexpression of the Slug, indicating increased mesenchymal-epithelial conversion （MET）; and increased protein expression of PTEN, and declined protein expression of P-Akt. Conclusion： Simultaneously inhibiting the expression of XIAP and survivin can partially reverse EMT phenotype of pancreatic cancer Panc-1 cells, which then significantly reduces the cell invasion and migration of Panc-1 cell lines. This process may be regulated by PTEN/P13K/Akt signaling pathway.