Glutamine 1 regulates the chemosensitivity of intrahepatic cholangiocarcinoma cells to 5-FU by targeting major vault protein / 中华普通外科杂志

ABSTRACT

Objective To study the functions and mechanisms of glutamine 1 (GLS1) in intrahepatic cholangiocarcinoma (ICC) cell to 5-fluorouraeil (5-FU) chemosensitivity.Methods The expression and relation between GLS1 and major vault protein (MVP) in cholangiocarcinoma were analyzed by bioinformatics database.Western blot and immunohistochemistry were used to detect the expression of GLS1 and MVP in 42 ICC tissues,and the correlation between GLS1 and MVP was studied by statistics.The regulation of GLS1 in ICC cell were evaluated by siRNA interference and pcDNA overexpression,and then tested the interference and overexpression efficiency of GLS1 by Western blotting.The chemosensitivity to 5-Fu was tested by cell counting kit-8 (CCK-8).Results The expression of GLS1 and MVP in ICC tissues was significantly up-regulated (tGLSI =3.963;tMVP =3.131,P ＜ 0.05),and the expression of GLS1 was positively correlated with MVP(r2 =0.351 7,P ＜ 0.05).Knockdown of GLS1 in QBC939 cells enhanced chemosensitivity of QBC939 cells to 5-Fu and notably downregulated MVP expression,while enforced expression of GLS1 in RBE cells promoted MVP expression and reduce cell sensitivity to 5-fluorouracil chemosensitivity.Conclusions GLS1 regulates the chemosensitivity of ICC cells to 5-Fu,and its mechanism may relates to the regulation of MVP.