| Backgroud:Xiaoai jiedu Prescription(XJP) was submitted by master of chinese medicine Zhou zhongying, according with his years of clinical experience in treatment on malignant tumor. A variety of clinical andExperimental studies explored XJP was treated on malignant tumor and verified its excellent effects. However, the study based on metabonomic, charactered by holistic concept in accordence with chinese medicine was not applied. So the aim of this study was to explore the antitumor effects and mechanism of XJP.Objective:.In this study, modern research techniques were used to evaluate the survival state including appetite and weight change,to find pathology changes and immune mechanism, to investigate the abnormal metabolic changes in rats with W256 sarcocarcinoma and the mechanism of XJP on anti-tumor based on metabonomics.Methods:W256-transplanted tumor bearing rats models were established and were divided into control group, tumor model group and XJP treatment groups (10,30,90 g/kg), and cisplatin treatment group. In different groups, the weight and food intake of rats were observed. Enzyme-linked immunosorbent assay (ELISA):ELISA was employed to confirm the expression level of TNF-α and TGF-β VEGF and MMP-2 in serum derived from rats model of different groups. And pathology changes of transplanted tumor tissues in different groups were examined by H-E staining.Metabolomic finger printing of control group, model group and XJP treatment groups (10,30,90 g/kg), was acquired by GC-MS. Multivariate data statistic (PCA, PLS-DA,) was used to pattern recognition. Then we got the plasma and urine metabolic profiles belonged to 5 groups rats on 3 different time. The endogenous metabolites were assayed by NIST data base and other document. Then we compare the data group between groups to search the different metabolites (potential molecular markers) in plasma and urine between control group and model group.meanwhile analysize metabolic pathway on internet. Further to campare the different metabolites between XJP treatment groups with model group to filter out the biomarker of XJP working.Results:Compared with control group, the appetite and weight of rats in different XJP groups can be improved campared with the cisplatin group and model group. Also the level of TNF-α TGF-β VEGF and MMP-9 in serum derived from rats were significantly reduced by XJR. And still, high-dose XJP group and the cisplatin group inhibited growth of W256 transplanted tumors.Compared with the contrast group,30 endogenous metabolites significantly changed in rats plasma on third time point connected with glucose metabolic, amino acid metabolic,urea cycle;which indicated that these metabolites were associated with tumor growing.Throuth T-test,15 metabolites were filterd out changed largely,tyrosine,uracil,1H-indole-3-propanoic acid had similar change trend on first and third time point. Especially uracil, lH-indole-3-propanoic acid changed siganificantly with time went by, which could be potential metabolic biomarkers for diease developing.endogenous plasma metabolites on XJP groups only high dose group significantly changed on third time point, the containt of lysine, tryptophan, 1H-indole-3-propanoic acid, glutamine, inositol, orinthine, palmileic, alpha-glycerophos phate were lifted while the containt of pyruvic, cholesterolwere reduced by XJP.Compared with the contrast group,30 endogenous metabolites significantly changed in rats urine on third time point connected with glucose metabolic,amino acid metabolic,urea cycle; the obvious different metabolites were 5-hydroxyhexanoic acid, thymine, ribitol, oxidized dithioerythritol, uric acid, maltose, which were adjusted by high dose XJP so the six metabolites could be ranked as biomarkers for diease developing and drug effect.Conclusion:1, XJR groups inhibited tumor growth of W256 transplanted tumors and improve the appetite and weight of rats in different XJP groups, which was likely resulted from its inhibition on TNF-a TGF-B MMP-9 and VEGF expression.2, Metabolites of plasma and urine of W256 tumor bearing rats significantly changed after tumor planting. The biomarkers for diease developing were searched out. Also metabolic pathway associated with changed metabolites were filterd out on internet3, Abnormal metabolite levels in plasma and urine can be partly recovered by XJR, and the potential antitumor effects of XJR may be contributed to the regulation of related metabolic pathways. |
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