中国现代普通外科进展2024,Vol.27Issue(4) :264-269.DOI:10.3969/j.issn.1009-9905.2024.04.003

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 cholangiocarci-noma cells by regulating YAP/TAZ signal pathway

严雨薇 施文 胡丹
中国现代普通外科进展2024,Vol.27Issue(4) :264-269.DOI:10.3969/j.issn.1009-9905.2024.04.003

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 cholangiocarci-noma cells by regulating YAP/TAZ signal pathway

严雨薇 1施文 2胡丹2
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作者信息

  • 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)
  • 折叠

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.

Abstract

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

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出版年

2024
中国现代普通外科进展
山东大学

中国现代普通外科进展

CSTPCD
影响因子:0.993
ISSN:1009-9905
参考文献量14
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