Effect and Mechanism of Wumeiwan Against Lewis Lung Cancer in Mice with Syndrome of Cold and Heat in Complexity Based on HGF/C-Met Signaling Pathway / 中国实验方剂学杂志

ABSTRACT

ObjectiveTo investigate the effect and mechanism of Wumeiwan against Lewis lung cancer in mice with syndrome of cold and heat in complexity based on hepatocyte growth factor/mesenchymal-epithelial transition factor （HGF/C-Met） signaling pathway. MethodTwenty healthy male mice were classified into blank group， model group （equivalent volume of distilled water， ig）， cisplatin group （4.0 mg·kg-1 cisplatin， ip）， and Wumeiwan group （12.5 mL·kg-1 Wumeiwan， ig）， with 5 in each group. Lewis lung cancer with the syndrome of cold and heat in complexity was induced in mice except the blank group by gavage of propylthiouracil， Zhimu Shigaotang， and Fanxieye， ice-water swimming， and subcutaneous injection of dry yeast suspension and Lewis cell suspension under the right armpit. After modeling， administration began and lasted 6 weeks. After the experiment， the tumor weight， tumor volume， tumor inhibition rate， and lung cancer metastasis-inhibiting proportion were measured and calculated. The pathological morphology of lung tissue was observed based on hematoxylin and eosin （HE） staining. The growth state of tumor tissue was analyzed by immunohistochemistry. The mRNA expression of HGF and C-Met was detected by Real-time polymerase chain reaction （PCR）， and the protein expressions of HGF， C-Met， survivin， and X-linked inhibitor of apoptosis protein （XIAP） by Western blot. ResultCompared with the blank group， the model group showed high mRNA expression of HGF and C-Met and protein expression of HGF， C-Met， surviving， and XIAP （P<0.01）. Compared with the model group， Wumeiwan group displayed low proportion of positive cells， positive cell density， positive score （P<0.05）， histochemical score， tumor weight， tumor volume （P<0.01）， mRNA expression of HGF and C-Met （P<0.01）， and protein expression of HGF， C-Met， surviving， and XIAP （P<0.01）. Compared with the model group， the cisplatin group displayed decrease in the proportion of positive cells， density of positive cells （P<0.05）， positive score， tumor weight， tumor volume （P<0.01）， mRNA expression of HGF and C-Met （P<0.01）， and protein expression of HGF， C-Met， surviving， and XIAP （P<0.01）， and insignificant variation in the histochemical score. Wumeiwan group had high mRNA expression of HGF （P<0.01）， and insignificant variation in the proportion of positive cells， positive cell density， histochemical score， positive score， tumor weight， tumor volume， mRNA expression of C-Met， and protein expression of HGF， C-Met， surviving， and XIAP. ConclusionWumeiwan can slow down the progression of Lewis lung cancer in mice with syndrome of cold and heat I complexicity by inhibiting HGF/C-Met signaling pathway.