Inhibition of Total Flavonids from Cudrania tricuspidata Bun on Lewis Lung Cancer and the Effect of Its Component Compatibility on Autophagy of LLC Cells / 中国药学杂志

ABSTRACT

OBJECTIVE: To explorethe effect of total flavonoids from Cudrania tricuspidata Bun on Lewis lung cancer mice and its new component compatibility on the autophagy of LLC cells. METHODS: A mouse model of Lewis lung cancer xenografts was constructed. The body weight, tumor weight, tumor volume and organ index were measured before and after taking total flavonoids of Cudrania tricuspidata Bun. The HE staining of the xenograft pathological sections were also observed. The TNF-α, IL-2, IL-6 and IL-12 levels in the serum were calculated by ELISA. The content of the main active ingredient and its ratio in the flavonoid extract were measured by UPLC. Western blot was used to detect the effect of the new component compatibility on the expression of autophagy protein in LLC cells, and the ultra structural changes of LLC cells were observed by transmission electron microscopy. Flow cytometry was used to detect the effect of the new component compatibility on autophagy of LLC cells. RESULTS: The high-dose group of total flavonoids from Cudrania tricuspidata Bun can significantly inhibit the growth of tumor in mice and enhance the organ index of tumor-bearing mice, and the survival rate of mice could be improved in all groups of total flavonoids from Cudrania tricuspidata Bun. The serum levels of TNF-α, IL-2, IL-6 and IL-12 in the tumor-bearing mice of each group were higher than those in the model group, and there was significant difference in the high dose group of total flavonoids (P<0.01). The main active ingredients were taxifolin, kaempferol and naringenin by UPLC. The ratio of taxifolin to kaempferol was 601. Western blot assay showed that its new component compatibility significantly increased the expression of autophagic protein in LLC cells (P<0.01). The autophagosomes in the cytoplasm were observed by transmission electron microscopy. The results of flow experiments showed that the average fluorescence intensity of its new component compatibility was significantly higher than that of the control group. CONCLUSION: Total flavonoids of Cudrania tricuspidata Bun can effectively inhibit tumor growth and have less harm to immune organs. Its mechanism may be related to up-regulation of cytokines TNF-α, IL-2, IL-6 and IL-12 levels and improve immune function in the body. Moreover, its main active ingredient promotes the increase of autophagy protein expression in LLC cells and induces autophagy in LLC cells.