Objective:To investigate the effect of vitamin K2(VK2)on the chemotherapy resis-tance 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-fluo-rouracil(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 cy-tometry.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 ex-pression 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
Key words
Cholangiocarcinoma/Vitamin K2/Yes-associated protein/transcriptional co-activa-torwith PDZ-binding motif signal pathway/Chemotherapy resistance