白藜芦醇通过调节Hippo信号通路抑制胰腺星状细胞活化

Resveratrol inhibits pancreatic stellate cell activation through modulating the Hippo signal pathway

目的探讨白藜芦醇对胰腺星状细胞活化的影响及Hippo信号通路的作用。方法组织块胰酶消化法提取原代胰腺星状细胞,给予白藜芦醇干预胰腺星状细胞,Westernblot、免疫荧光染色检测胰腺星状细胞活化的指标,Transwell侵袭实验及Westernblot检测间接共培养条件下胰腺癌细胞Panc-1侵袭能力及EMT指标E-cadherin,Vimentin的变化。结果白藜芦醇能够抑制胰腺星状细胞的活化,抑制α-SMA及YAP、CTGF及CYR61的表达;白藜芦醇干预后的胰腺星状细胞上清与胰腺癌细胞共培养后,Panc-1细胞侵袭能力降低(P<0.05),E-cadherin表达升高,Vimentin表达降低(P<0.05)。结论白藜芦醇能够抑制胰腺星状细胞活化,并降低共培养条件下胰腺癌细胞Panc-1的侵袭能力和EMT转化。

Objective To investigate the inhibitory effect of resveratrol on the activation of pancreatic stellate cells and to explore the role of the Hippo signaling pathway in it. Methods Pancreatic stellate cells (PSCs) were isolated by trypsin digestion and then treated with resveratrol. Western blot and immunofluorescence staining were used to detect the activation of the cells. Transwell invasion assay and Western blot were used to detect the invasive ability of Panc-1 and the expressions of E-cadherin and Vimentin in pancreatic cancer cells (PCs)-PSCs indirect co-culture conditions. Results Resveratrol could inhibit the activation of PSCs and inhibit YAP,CTGF and CYR61 expressions. After co-culture with PSCs condition medium pre-treated with resveratrol, the invasive ability of Panc-1 cells was significant reduced ( P <0.05). E-cadherin expression was increased while Vimentin expression was decreased ( P <0.05). Conclusion Resveratrol can inhibit the activation of pancreatic stellate cells via inhibiting YAP expression and can also inhibit the invasion and EMT transformation of Panc-1 cells under co-culture conditions.