Objective To investigate the effects of Sennoside A(SA)on the proliferation,migra-tion,invasion,glycolysis and other malignant biological behaviors of gallbladder carcinoma cells,and to analyze the related mechanisms.Methods Human gallbladder carcinoma cell lines,NOZ and SGC-996,were cultured in vitro and divided into control group,SA low dose group(L-SA,25 µmol/L),SA medium dose group(M-SA,50 μmol/L)and SA high dose group(H-SA,100 µmol/L),and H-SA+phosphati-dylinositol 3-kinase/protein kinase B(PI3K/AKT)signaling pathway activator 740Y-P group,respectively.The proliferation,migration,invasion,apoptosis and glycolysis of gallbladder cancer cells in each group were detected by cell counting assay,Transwell,flow cytometry and glycolysis kit.The protein levels of PI3K,p-PI3K,AKT and p-AKT were detected by Western blot assay.NOZ cells were used to construct tumor model of nude mice,and the mice were divided into saline treatment group and 10 mg/kg SA treat-ment group.The tumor formation ability of the two groups of mice was compared,and the expression level of Ki-67 in tumor of the two groups was detected by immunohistochemical assay.Results Compared with con-trol group,the proliferation,migration,invasion,glycolysis ability,the expression levels of p-PI3K and p-AKT were significantly decreased in SA treatment groups,while the apoptosis level was significantly up-regulated,all differences were statistically significant(P＜0.05).Compared with H-SA group,the prolifer-ation,migration,invasion and glycolysis of H-SA+740Y-P group cells were up-regulated,while the apopto-sis level was significantly decreased,all differences were statistically significant(P＜0.05).In vivo tumori-genesis experiments showed that,compared with the control group,the tumor volume of the SA-treated mice was reduced at day 28[(1 051.32±130.29)mm3 vs(575.07±170.54)mm3,P=0.0003),the tumor weight was reduced[(1.04±0.24)g vs(0.58±0.13)g,P=0.0019],and the average optical density of Ki-67 expression was reduced[(77.00±7.00)vs(33.33±7.51),P=0.0018].Conclusion SA can inhibit the proliferation,migration,invasion and glycolysis of gallbladder carcinoma cells by regulating PI3K/AKT pathway.
Gallbladder neoplasmsSennoside APhosphatidylinositol 3-kinase/kinase B path-wayGlycolysis
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