蜥蜴胃康方对胃癌浸润转移的干预作用及机制研究

Effect of the Lizard Weikang prescription on the expression of EMT related protein in nude mice with liver metastasis of gastric cancer

目的研究不同浓度蜥蜴胃康方对胃癌肝转移模型裸鼠上皮间质转化(EMT)相关蛋白的影响,探讨蜥蜴胃康方对胃癌肝转移的调控机制。方法70只SPF级BALB/c裸鼠,随机分为空白对照组、模型对照组、5-FU对照组、华蟾素片对照组以及蜥蜴胃康方高、中、低浓度组。除空白对照组外,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,药物治疗组分别以5-FU,华蟾素,蜥蜴胃康方高、中、低浓度中药汤剂连续治疗4周。HE染色观察胃癌肝转移模型裸鼠肝组织病理学变化;免疫组化法检测肝组织MUC-5A表达水平;Western-blot检测EMT相关蛋白E-cadherin、Integrinβ1、MMP9的表达情况。结果蜥蜴胃康方可以降低胃癌肝转移裸鼠肝组织中MUC-5A表达水平(P<0.05),抑制其肝脏中Integrinβ1、MMP9蛋白表达(P<0.05),促进E-cadherin蛋白表达(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。结论蜥蜴胃康方可以通过调控胃癌肝转移裸鼠肝组织中E-cadherin、Integrin、MMP-9蛋白表达而抑制EMT,从而达到有效干预胃癌肝转移的目的。

Objective To study the effects of different concentrations of Lizard Weikang decoction on EMT related proteins in nude mice with liver metastasis of gastric cancer,and to explore the regulatory mechanism of Lizard Weikang decoction on liver metastasis of gastric cancer.Methods 70 SPF BALB/C nude mice were randomly divided into blank control group,model control group,5-FU control group,cinobufagin control group and Lizard Weikang decoction high,medium and low concentration groups.In addition to the blank control group,the mice in 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 for 4 weeks.The liver histopathological changes of nude mice with liver metastasis of gastric cancer were observed by HE staining;the expression of MUC-5 A in liver tissue was detected by immunohistochemistry;the expressions of EMT related proteins E-cad,integrinβ1 and MMPs were detected by Western blot.Results Lizard Weikang decoction could reduce the expression level of MUC-5 A in liver tissue of nude mice with liver metastasis of gastric cancer(P<0.05)and inhibit integrinβ1 and MMP9 protein expression in liver(P<0.05),promote the expression of E-cadherin protein(P<0.05),and have a certain repair effect on the liver tissue of nude mice with liver metastasis of gastric cancer.Conclusion Lizard Weikang decoction can through inhibit EMT by regulating the expression of E-cadherin,integrin and MMP-9 proteins in nude mice with liver metastasis of gastric cancer to effectively intervene the liver metastasis of gastric cancer.