BCKDK通过激活Wnt/β-catenin信号通路调控子宫内膜癌细胞的增殖与凋亡OA

Aim To investigate the effect of branched-chain α-keto acid dehydrogenase kinase(BCKDK)on the proliferation and apoptosis of endometrial cancer cells through the Wnt/β-catenin signaling pathway.Methods The mRNA and protein expression levels of BCKDK in endometrial cancer tissues,adjacent normal tissues,normal endometrial epithelial cells,and en-dometrial cancer cell lines(HEC-1-A and Ishikawa)were detected by quantitative real-time PCR and Western blotting.A BCKDK-knockdown endometrial cancer cell model was established using lentiviral infection.Cell viability was analyzed by CCK-8 assay,ap-optosis was detected by flow cytometry,and the protein expression levels of CyclinD1,CDK2,caspase-3,caspase-9,Wnt3a,and β-catenin were measured by Western blotting.The Wnt/β-catenin signaling pathway activator LiCl was added to BCKDK-knockdown cells to observe its effect on proliferation and apoptosis.Results BCKDK mRNA expression was significantly higher in endometrial cancer tissues than that in adjacent normal tissues(P<0.05).BCKDK mRNA levels varied significantly with tumor dif-ferentiation,clinical stage,and lymph node metastasis(P<0.05).Both HEC-1-A and Ishikawa cell lines showed significantly ele-vated BCKDK mRNA and protein expression compared with normal endometrial epithelial cells(P<0.05).Compared with the nega-tive control group,the shBCKDK group exhibited decreased BCKDK expression,cell viability,CyclinD1,CDK2,Wnt3a,and β-cate-nin protein levels,as well as increased apoptosis and elevated caspase-3 and caspase-9 expression.However,these effects were sig-nificantly reversed by LiCl treatment in the shBCKDK+LiCl group(P<0.05).Conclusion BCKDK is highly expressed in endo-metrial cancer cells.Downregulation of BCKDK inhibits proliferation and promotes apoptosis of HEC-1-A and Ishikawa cells,possibly through the regulation of Wnt/β-catenin signaling pathway.