白藜芦醇对胰腺癌细胞增殖和凋亡影响的研究

Study on the Effects of Resveratrol on Proliferation and Apoptosis of Pancreatic Cancer Cells

为了研究白藜芦醇对人胰腺癌细胞增殖和存活的影响,利用不同浓度白藜芦醇处理PANC-1和Bx PC-3细胞,通过MTS和软琼脂集落实验检测白藜芦醇对胰腺癌细胞的停泊依赖和停泊非依赖增殖的抑制。同时,采用免疫印迹的方法,检测不同浓度白藜芦醇对胰腺癌细胞增殖相关信号通路的调控,及不同时间点凋亡激活相关蛋白分子的表达。结果发现白藜芦醇能剂量依赖性抑制PANC-1和Bx PC-3细胞增殖,并且这种增殖抑制作用与表皮生长因子受体(epithelial growth factor receptor,EGFR)及下游信号通路的抑制有关。一定浓度的白藜芦醇能诱导胰腺癌细胞发生凋亡,caspase3和caspase7被剪切活化。通过检测Bcl-2(B-cell lymphoma-2,Bcl-2)促存活家族蛋白,证实白藜芦醇能有效抑制Mcl-1(myeloid cell leukemia-1,Mcl-1)的表达,并不改变Bcl-2和Bcl-XL的表达。实验结果初步表明,白藜芦醇抑制胰腺癌的增殖与存活与EGFR信号通路及促存活蛋白Mcl-1的表达下调有关。

To investigate the effects of resveratrol on proliferation and apoptosis of human pancreatic cancer cells, PANC-1 and Bx PC-3 cells were treated with various concentrations of resveratrol for different time points, the proliferation was evaluated by MTS and soft agar assay. Meanwhile, the signaling transduction pathway after resveratrol treatment and the expression of the protein which involved in apoptosis were tested via immunoblotting. The results showed that resveratrol inhibited the proliferation of PANC-1 and Bx PC-3cells in a dose-dependent manner. Moreover, the effects of resveratrol mediated proliferation inhibition of pancreatic cancer cells was related to the suppression of epithelial growth factor receptor（EGFR） signaling pathway. Additionally, a certain concentration of resveratrol can directly induce apoptosis in pancreatic can-cer cells, which result in the activation of caspase3/caspase7 and down-regulation of the expression of myeloid cell leukemia-1（Mcl-1）. The primary data demonstrated that the suppression of EGFR signaling path-way and down-regulation of Mcl-1 expression are involved in resveratrol mediated proliferation inhibition in pancreatic cancer cells.