Anti-Tumor Mechanism Study Of Matrine Via Inhibiting The Lipid Synthesis Through Regulating SREBP Pathways

Objective The aim of this study is to investigate the anti-tumor mechanism of matrine inhibiting lipid synthesis of tumor cells through regulating sterol regulatory element-binding proteins(SREBP)pathways.MethodsIn vivo experiments: CT26 cells were implanted under the skin of mice to establish tumor xenograft animal models.The tumor-bearing mice were divided into model,positive control,treatment with low dosage or high dosage of matrine groups respectively.After CT26 cell injection,mice in each group were orally treated with normal saline,cyclophosphamide and different dosages of matrine respectively.The tumor tissue was weighed and stained with HE to study the anti-tumor effect of matrine on colon tumor-bearing mice.Moreover,qPCR was performed to investigate the expression of ATP-citrate lyase(ACLY),acetyl-Co A carboxylase(ACC)and fatty acid synthase(FASN)in tumor tissue.In vitro experiments: MTT assay was used to investigate the effect of matrine on the proliferation of CT26 cells;levels in lipid accumulation in CT26 cells after matrine treatment were detected by oil red O staining and free fatty acid(FFA)detection kit.The relative expressions of lipid metabolism-related genes in tumor cells were detected by qPCR,and the expressions of SREBP1,ACLY,ACC and FASN proteins in CT26 cells after treatment with matrine were detected by Western-blot.Results 1)The results of animal experiments showed that compared with the model group,both the low dosage and high dosage of matrine groups could significantly reduce the tumor weight of the tumor-bearing mice.Oil red O staining and FFA detection demonstrated that the tumor tissues of Low-dose matrine and High-dose matrine groups decreased lipid accumulation.qPCR results showed that matrine could decrease the gene expression level of ACLY?ACC?FASN in tumor tissue.2)MTT assay showed that matrine effectively inhibited the proliferation of CT26 cells at a minimum concentration of 0.4 ?mol/ml for 48 hours.Oil red O staining and FFA detection demonstrated that matrine decreased lipid accumulation in CT26 cells.Moreover,the expression of SREBP related genes and proteins were down-regulated after treatment with matrine in CT26 cells.ConclusionMatrine inhibites tumor growth in tumor-bearing mice.The anti-tumor mechanisms of matrine in inhibiting the lipid synthesis maybe through regulating SREBP pathways.