熊果苷调节PI3K/Akt/GLUT1信号通路对胃癌细胞恶性进展的影响  

Effect of arbutin on the malignant progression of gastric cancer cells by regulating the PI3K/Akt/GLUT1 signaling pathway

作　　者：韩玲 蔚晓勇 郭秀春[1] HAN Ling;WEI Xiaoyong;GUO Xiuchun(Department of Medical Oncology,Bayannur Hospital,Inner Mongolia,Bayannur 015000,China)

机构地区：[1]内蒙古自治区巴彦淖尔市医院肿瘤内科,015000

出　　处：《河北医药》2024年第13期1925-1929,共5页Hebei Medical Journal

基　　金：内蒙古医科大学联合计划项目(编号:YKD2021LH100);巴彦淖尔市科技计划项目(编号:KY202155)。

摘　　要：目的 探讨熊果苷(Arb)调节磷脂酰肌醇-3激酶B/蛋白激酶B/葡萄糖转运蛋白1(PI3K/Akt/GLUT1)信号通路对胃癌细胞恶性进展的影响。方法 使用不同浓度(12.5、25、50、100、200、400 mol/L)Arb处理SNU-601细胞,检测细胞活性,筛选最佳浓度;将细胞分为对照组(Control组)、熊果苷低、中、高浓度组(L-Arb组、M-Arb组、H-Arb组)、熊果苷高浓度+PI3K/Akt激活剂组(H-Arb+740 Y-P组),分别检测细胞凋亡率、细胞周期、葡萄糖摄取、乳酸生成、ATP生成、细胞迁移数和细胞侵袭数;Western blot检测Bax、半胱氨酸天冬氨酸蛋白水解酶3(cleaved-caspase3)、B细胞淋巴瘤-2(Bcl-2)、p-PI3K、PI3K、p-Akt、Akt、GLUT1、HKⅡ蛋白表达。结果 12.5~400 mol/L的Arb可显著抑制SNU-601细胞增殖,选择50、100、200 mol/L的Arb进行后续实验。与Control组比较,L-Arb组、M-Arb组、H-Arb组细胞活性、葡萄糖摄取、乳酸生成、ATP生成、细胞迁移数、细胞侵袭数及Bcl-2、p-PI3K/PI3K、p-Akt/Akt、GLUT1、HKⅡ蛋白表达降低,细胞凋亡率和Bax、cleaved-caspase3蛋白表达增加(P<0.05);与H-Arb组比较,H-Arb+740 Y-P组细胞活性、葡萄糖摄取、乳酸生成、ATP生成、细胞迁移数、细胞侵袭数及Bcl-2、p-PI3K/PI3K、p-Akt/Akt、GLUT1、HKⅡ蛋白表达增加,细胞凋亡率和Bax、cleaved-caspase3蛋白表达降低(P<0.05)。结论 Arb通过抑制PI3K/Akt/GLUT1信号通路抑制胃癌细胞恶性进展。Objective To investigate the effect of arbutin(Arb)on malignant progression of gastric cancer cells by regulating the phosphatidylinositol 3 kinase/threonine protein kinase/glucose transporter 1(PI3K/Akt/GLUT1)signaling pathway.Methods SNU-601 cells were treated with different concentrations of Arg(12.5,25,50,100,200,400μmol/L),and cell activity was measured to screen the optimal concentration.SNU-601 cells were induced with blank control,low-dose,medium-dose and high-dose Arb,and high-dose Arb+PI3K/Akt activator 740 Y-P.Apoptotic rate,cell cycle,glucose uptake,lactate production,ATP production,cell migration and cell invasion were detected.Western blot was applied to detect the protein expressions of Bax,cleaved-caspase3,Bcl-2,p-PI3K,PI3K,p-Akt,Akt,GLUT1,and HKⅡ.Results Treatment of 12.5-400μmol/L Arg significantly inhibited the proliferation of SNU-601 cells.50,100,and 200μmol/L of Arg were selected for the low-dose,medium-dose and high-dose in the subsequent experiments.Compared with those of blank control,SNU-601 cells induced with low-dose,medium-dose and high-dose Arb presented significantly lower cell viability,glucose uptake,lactate production,ATP production,migratory and invasive cell number,and protein levels of Bcl-2,p-PI3K/PI3K,p-Akt/Akt,GLUT1 and HKⅡ,but higher apoptotic rate and protein levels of Bax and cleaved-caspase 3(P<0.05).Compared with high-dose Arb-induced cells,those induced with high-dose Arb+740 Y-P presented significantly higher cell viability,glucose uptake,lactate production,ATP production,migratory and invasive cell number,and protein levels of Bcl-2,p-PI 3K/PI3K,p-Akt/Akt,GLUT1 and HKⅡ,but lower apoptotic rate and protein levels of Bax and cleaved-caspase 3(P<0.05).Conclusion Arb inhibits the malignant progression of gastric cancer cells by inhibiting the PI3K/Akt/GLUT1 signaling pathway.

关 键 词：熊果苷 磷脂酰肌醇-3激酶/苏氨酸蛋白激酶/葡萄糖转运蛋白1信号通路 胃癌 糖酵解 恶性进展 

分 类 号：R735.2[医药卫生—肿瘤]