大泻脾汤调控FOXK1有氧糖酵解对胃癌荷瘤小鼠的影响OA

Objective To investigate the effects of Daxiepi Decoction(大泻脾汤,DXPD)on gastric cancer-bearing mice via regulat-ing FOXK1 and aerobic glycolysis.Methods A gastric cancer xenograft mouse model was established.Seventy C57BL/6 mice were ran-domly divided into seven groups(n=10 per group):normal control,model control,low/medium/high-dose DXPD(2.93 g·kg⁻1·d⁻1,5.85 g·kg⁻1·d⁻1,11.7 g·kg⁻1·d⁻1),oxaliplatin(10 mg·kg⁻1),and 2-DG(1 g·kg⁻1·d⁻1).Protein expression of glycolysis-related markers including forkhead box K1(FOXK1),hexokinase 2(HK2),glucose transporter 1(GLUT1),pyruvate kinase M2(PKM2),and lac-tate dehydrogenase A(LDHA),as well as apoptosis-related proteins(Bcl-2,Bax,Caspase-3),was detected by Western blot(WB).Immunofluorescence(IF)was used to assess Ki67 and GLUT1 levels.Tumor mass was measured.Apoptosis rate was analyzed by flow cytometry(FCM).Ultrastructural changes in tumor cells were observed by electron microscopy.Results Compared with the normal group,the model group showed decreased body weight(P<0.05).Compared with the model group,all treatment groups exhibited sig-nificant inhibition of tumor growth,increased body weight,and reduced tumor mass(P<0.05).The apoptosis rate was significantly increased in all treatment groups(P<0.05).IF analysis showed decreased expression of Ki67 and GLUT1 in tumor tissues of the treat-ment groups.WB analysis showed that expression levels of FOXK1,HK2,PKM2,LDHA,and Bcl-2 were significantly decreased(P<0.05),while levels of Bax and Caspase-3 were increased(P<0.05).Conclusion DXPD can inhibit tumor growth and promote apopto-sis in gastric cancer-bearing mice,which may be achieved by reducing FOXK1 protein levels,thereby inhibiting aerobic glycolysis.