β-细辛醚对胃癌裸鼠上皮间质转化的影响

Effects of β-asarone on Epithelial-Mesenchymal Transition of Gastric Cancer in Nude Mice

目的观察β-细辛醚对人胃癌MGC-803细胞BALB/c裸鼠皮下移植瘤上皮间质转化(epithelialmesenchymal transition,EMT)的影响并探讨其分子机制。方法将胃癌MGC-803细胞接种于裸鼠皮下制备移植瘤模型。随机分为阴性对照组(模型组)、阳性对照组(5-FU组,25 mg/kg)、β-细辛醚高剂量组(100mg/kg)、低剂量组(50 mg/kg),每组8只,各组灌胃给药,每日1次,连续用药10日。干预结束后处死小鼠,计算抑瘤率;通过实时定量PCR及Western Blot法检测移植瘤中EMT上皮型标志物E-钙黏蛋白(E-cadherin)、间质型标志物N-钙黏蛋白(N-cadherin)、转录因子Snail以及磷脂酰肌醇3-激酶(phosphatidylinositol3-kinase,PI3K)、磷酸化磷脂酰肌醇3-激酶(phosphorylation of phosphatidylinositol 3-kinase,p-PI3K)、丝氨酸-苏氨酸激酶(serine/threonine kinase,AKT)、磷酸化丝氨酸-苏氨酸激酶(phosphorylation of serine/threonine kinase,p-AKT)的表达。结果与模型组比较,5-FU组、β-细辛醚高、低剂量组第7~11日移植瘤体积明显缩小(P<0.05),N-cadherin、Snail、p-AKT、p-PI3K蛋白及m RNA表达降低(P<0.05),E-cadherin蛋白及m RNA表达升高(P<0.05)。结论β-细辛醚对胃癌细胞增殖能力有抑制作用,其机制可能与下调胃癌细胞的PI3K/AKT信号通路,抑制胃癌细胞EMT有关。

Objective To observe the effects of 13-asarone on epithelial-mesenchymal transition （EMT） of human gastric cancer MGC-803 cells in BALB/c nude mice,and to study its possible molecular mechanism. Methods Gastric cancer MGC-803 cells were subcutaneously inoculated to nude mice for preparing transplanted tumor model. Totally 24 nude mice were then divided into the negative control group （model）, the positive control group （5-FU,25 mg/kg）, the high dose β-asarone group （100 mg/ kg）, the low dose β-asarone group （50 mg/kg）, 8 in each group. Corresponding medicines were adminis- tered to rats in respective group by gastrogavage, once per day for 10 successive days. The mice were sacrificed at the end of the intervention, and the tumor inhibition rate was calculated. The expressions of E-cadherin, N-cadherin, Snail, phosphatidylinositol 3-kinase （PI3K）, phosphorylation of phosphatidyli- nositol 3-kinase （p-PI3K）, serine/threonine kinase （AKT）, phosphorylation of serine/threonine kinase （p-AKT） were detected by Real-time PCR and Western Blot. Results Compared with the model group, the volume of transplanted tumor was obviously reduced in 5-FU group and 13-asarone groups from day7 to day 11 （P〈0.05）. Protein and mRNA expressions of N-cadherin, Snail, p-PI3K, p-AKTdecreased, and protein and mRNA expressions of E-cadherin increased in 5-FU group and β-asarone groups （P 〈 0.05）. Conclusions 13-asarone could inhibit proliferation ability of gastric cancer cells, and its mecha- nism might be associated with down-regulating PI3K/AKT signal pathway of gastric cancer cells and re-straining EMT of gastric cancer cells.