基于HIF-1α介导的PI3K/AKT信号通路的蜥蜴胃康方干预胃癌肝转移的作用及机制

Effect and mechanism of lizard Weikang decoction on liver metastasis of gastric cancer based on HIF-1αmediated PI3K/AKT signaling pathway

目的基于缺氧诱导因子(HIF)-1α介导的磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B(AKT)信号通路,研究不同浓度蜥蜴胃康方对胃癌肝转移的干预作用,并探讨其作用机制。方法70只SPF级BALB/c裸鼠,随机分为空白组、模型组、5-氟尿嘧啶(FU)组、华蟾素片组及蜥蜴胃康方高、中、低浓度组。除空白组外,其余各组均采用人胃癌HGC-27细胞悬液脾脏注射制备胃癌肝转移裸鼠模型。造模成功后,分别以5-FU、华蟾素、蜥蜴胃康方高、中、低浓度中药汤剂连续治疗4 w。苏木素-伊红(HE)染色观察胃癌肝转移模型裸鼠肝组织病理学变化;TUNEL检测胃癌细胞凋亡情况;Western印迹检测肝组织中HIF-1α、PI3K、p-AKT蛋白的表达情况。结果蜥蜴胃康方可以显著促进胃癌细胞凋亡(P<0.05),显著抑制胃癌肝转移模型裸鼠肝脏中HIF-1α、PI3K、P-AKT蛋白的表达(P<0.05),对胃癌肝转移模型裸鼠的肝脏组织有一定修复作用。结论蜥蜴胃康方能促进胃癌细胞凋亡,抑制胃癌肝转移,其机制可能与下调HIF-1α介导的PI3K/AKT信号通路上相关蛋白表达有关。

Objective Based on hypoxia-inducible factor(HIF)-1αmediated phosphatidylinositol-3 kinase(PI3K)/protein kinase B(AKT)signaling pathway to study the intervention effect and mechanism of different concentrations of lizard Weikang decoction on liver metastasis of gastric cancer.Methods 70 SPF BALB/c nude mice were randomly divided into blank group,model group,5-fluorouracil(FU)group,cinobufagin tablet group and lizard Weikang decoction high,medium and low concentrations groups.In addition to the blank group,other groups were used to prepare the nude mouse model of liver metastasis of gastric cancer by the method of spleen injection of human gastric cancer HGC-27 cell suspension.After the model was successfully established,it was treated with 5-FU,cinobufagin and lizard Weikang decoction of high,medium and low concentrations for 4 w.The liver histopathological changes of nude mice with liver metastasis model of gastric cancer were observed by hematoxylin-eosin(HE)staining;TUNEL was used to detect the apoptosis of gastric cancer cells;the expressions of HIF-1α,PI3K and p-AKT protein in liver tissue of nude mice were detection by Western blot.Results Lizard Weikang decoction could significantly promote the apoptosis of gastric cancer cells(P<0.05)and significantly inhibit the expressions of HIF-1α,PI3K and p-AKT protein in the liver of nude mice with gastric cancer liver metastasis model(P<0.05),which could repair the liver tissue of nude mice with liver metastasis model of gastric cancer.Conclusions Lizard Weikang decoction could promote the apoptosis of gastric cancer cells and inhibit liver metastasis of gastric cancer.Its mechanism might be related to the down regulation of the expressions of related protein in HIF-1αmediated PI3K/AKT signaling pathway.