维生素K2调节YAP/TAZ信号通路对胆管癌细胞化疗耐药性的影响  

Effect of vitamin K2 on chemoresistance of cholangiocarcinoma cells by regulating YAP/TAZ signal pathway

作　　者：严雨薇 施文[2] 胡丹[2] YAN Yu-wei;SHI Wen;HU Dan(Department of Clinical Nutritio,Nantong First People's Hospital,Nantong 226000,China;Department of General Surgery,Nantong First People's Hospital,Nantong 226000,China)

机构地区：[1]南通市第一人民医院临床营养科,江苏南通226000 [2]南通市第一人民医院普外科,江苏南通226000

出　　处：《中国现代普通外科进展》2024年第4期264-269,共6页Chinese Journal of Current Advances in General Surgery

摘　　要：目的:探究维生素K2(VK2)调节Yes相关蛋白(YAP)/PDZ结合基序转录共激活子(TAZ)信号通路对胆管癌(CCA)细胞化疗耐药性的影响。方法:将QBC939细胞设为对照组(Control组,空白培养基处理),QBC939/ADM细胞随机分为5-氟尿嘧啶(5-FU)耐药组、低浓度VK2组、中浓度VK2组、高浓度VK2组、高浓度VK2+YAP激活剂JASP组。CCK-8法检测细胞增殖能力。划痕实验检测细胞迁移能力。Transwell实验检测细胞侵袭能力。流式细胞术检测细胞凋亡。采用Western Blot检测凋亡相关蛋白Bax、Bcl-2、Caspase3和YAP/TAZ信号通路相关蛋白表达。结果:与Control组相比,5-FU组细胞OD450值(48 h、72 h)、细胞迁移率、细胞侵袭数目、细胞YAP、TAZ、Bcl-2蛋白表达显著上升(P<0.05),细胞凋亡率、细胞Bax、Caspase-3蛋白表达显著下降(P<0.05)。与5-FU组相比,VK2-M组、VK2-H组细胞的相应指标变化与上述相反(P<0.05)。JASP减弱了VK2逆转CCA化疗药物耐药性的作用。结论:VK2可能通过抑制YAP/TAZ信号通路,逆转CCA细胞对化疗药物的耐药性。Objective:To investigate the effect of vitamin K2(VK2)on the chemotherapy resistance of cholangiocarcinoma(CCA)cells by regulating the Yes-associated protein(YAP)/transcriptional co-activator with PDZ-binding motif(TAZ)signal pathway.Methods:The QBC939 cell was set as the Control group(blank medium treatment),QBC939/ADM cells were randomly divided into 5-fluorouracil(5-FU)resistant group(5-FU group),low concentration VK2 group,medium concentration VK2 group,high concentration VK2 group,and high concentration VK2+YAP activator JASP group.CCK-8 was used to detect the cell proliferation.Scratch test was used to detect cell migration.Transwell assay was used to detect the invasiveness of cells.Apoptosis was detected by flow cytometry.Western Blot was used to detect the expression of apoptosis related proteins Bax,Bcl-2,Caspase3 and YAP/TAZ signal pathway related proteins.Results:Compared with the control group,the cell OD 450 value(48 h,72 h),cell migration rate,number of cell invasion,and the expression of YAP,TAZ,Bcl-2 proteins in 5-FU group increased obviously(P<0.05),the apoptosis rate,and the expression of Bax and Caspase-3 proteins decreased obviously(P<0.05).Compared with 5-FU group,the changes of corresponding indicators of cells in VK2-M group and VK2-H group were contrary to the above(P<0.05).JASP attenuated the reversal effect of VK2 on CCA chemoresistance.Conclusion:VK2 may reverse the resistance of CCA cells to chemotherapy drugs by inhibiting YAP/TAZ signal pathway.

关 键 词：胆管癌 维生素K2 Yes相关蛋白/PDZ结合基序转录共激活子信号通路 化疗耐药 

分 类 号：R735.8[医药卫生—肿瘤]