Decylubiquinone And Lycium Barbarum Polysaccharide Inhibit Tumor Growth Via Inhibiting Angiogenesis Research

ObjectiveMalignant tumor has become a leading cause which threatens human health,and the main reason of failure cancer treatment is tumor metastasis,tumor vascular can provide kinds of nutrients for the growth of tumor cells,which plays an important role in tumor growth and metastasis,inhibiting tumor angiogenesis could inhibit tumor growth to reduce tumor metastasis.Decylubiquinone,which is caspase-9 inhibitor,is similar of coenzyme Q10 structure,with chicken embryos villi allantois membrane model(CAM)and the yolk sac membrane model(YSM).Previous research has shown that decylubiquinone could inhibit angiogenesis,QPCR assay showed BAI1 was up-regulated after HUVEC treated by decylubiquinone,there is little reports about decylubiquinone on anti-tumor and anti-tumor angiogenic effect,this study was to explore if decylubiquinone could anti-angiogenic to anti-tumor effect,and revealed its molecule mechanism of up-regulate BAI1 to act as an anti-angiogenic effect.lycium barbarum polysaccharide(LBP)that consist many kinds of monosaccharide has the anti-tumor,anti-aging,and other biological functions,with LBP treatment of liver cancer in mice previous research found the vascular endothelial growth factor(VEGF)of mice serum which treated with LBP was lower than that of control group.Via spontaneous breast cancer and colorectal cancer transplantation tumor model mice,this study was to investigate whether the LBP inhibit tumor angiogenesis and tumor growth and the mechanism of action.Methods1 Decylubiquinone inhibits tumor-induced angiogenesis through up-regulating the expression of BAI11.1 decylubiquinone effects on tumor-induced angiogenesis was detected by human colorectal model and mice colorectal cancer model.1.2 Matrix plug assay and rat arterial ring assay were detected to explore the effect of Dub anti-angiogenic in matrix.CCK8 assay were performed to detect cell proliferation effects of different concentration decylbiquinone treatment of human umbilical vein endothelial cells(HUVEC),skin vascular endothelial cells(HDMEC)and ocancer cells.1.3 After endothelial cells were treated with decylubiquinone 48h,the expression levels of BAI1 and p53 expression were detected by western blotting.If knocking down wild type p53 expression would regulated BAI1 expression was detected by siRNA experiment.2 Study of the lycium barbarum polysaccharide on inhibiting tumor angiogenesis2.1 MMTV-PyMT spontaneous breast cancer mouse model and colorectal cancer in mice model were treated by LBP to investigate the LBP effects on tumor angiogenesis.2.2 The rat arterial ring assay was detected to explore the effect of LBP on angiopoiesis.CCK8 assay were performed to detect cells proliferation effects of different concentration LBP treatment of umbilical vein endothelial cells(HUVEC),skin vascular endothelial cells(HDMEC)and cancer cell for 48 hours,BAI1 expression of HDMEC was detected via QPCR after LBP treatment.Results1 Decylubiquinone inhibits tumor-induced angiogenesis through up-regulating the expression of BAI11.1 Decyl ubiquinone has inhibitory effect on tumor growth in mice and tumor angiogenesisCompared the tumor volume and weight,the experimental results showed that decyl ubiquinone inhibits nude mice colorectal cancer and colorectal tumor growth in micec(P<0.05),immunohistochemical results show that compared to the control group,experimental group expressed less of CD31 in tumor tissues(P<0.05).1.2 Matrix plug experiment and rat arterial ring experiment found decylubiquinone could reduce blood vessel formationMatrix plug experiment showed that of blank group matrix were without blood vessel formation,there were blood vessel formation in the control group matrix,blood vessels of experimental group were relatively less than the control group,CD31 immunofluorescence assay results showed vascular density in the matrix were relatively less than the control group(P<0.05),Elisa kit results showed that hemoglobin content in the experimental group is lower than the control group(P<0.05).Rat arterial ring experimental results showed the experimental group blood vessels formed relatively less that of the control group(P<0.05),and the inhibition degree is correlated to the drug dose.CCK8 results showed decylubiquinone inhibited HUVEC proliferation,half killer drug concentration is 21.4 ?M,half killer drug concentration of HDMEC is 18.45 ?M.Decylubiquinone(0-100 u M)had no effect on HCT116 human colorectal cancer cells,lovo cells and mice CT26 colorectal cancer cell proliferation.1.3 BAI1,p53 expression increased by treatment of decylubiquinone on HDMECBAI1,p53 expression of HUVEC increased with decylubiquinone treatment,siRNA silencing HDMEC p53 expression,BAI1 expression reduced.2 Study of the LBP effects on inhibiting tumor angiogenesis2.1 The LBP inhibits tumor growth and tumor angiogenesis Compared the tumor size and treatment,the experimental result showed that LBP inhibits MMTV-PyMT tumor growth in mice and colorectal tumor growth in mice(P<0.05),immunohistochemical results showed that CD31 expression of the LBP group in tumor tissue were less than that of the control group(P<0.05).2.2 The effect of LPS on cell proliferation and angiopoiesisCCK8 assay showed LPS had no effect on HUVEC,HDMEC proliferation,neither did the MDA-MB-231 cells,4Tlcells and CT26 cells.rat arterial ring experiment result showed:LBP group blood vessels form were relatively less than that of the control group.BAI1 expression of HDMEC treated by LBP was up-regulated.Conclusion1 Decylubiquinone inhibits tumor-induced angiogenesis through up-regulating the expression of BAI11,1.1 Decylubiquinone could inhibit tumor angiogenesis and inhibit the growth of colorectal cancer.1.2 Decylubiquinone inhibited endothelial cell proliferation and angiogenesis,but had no influence on colorectal tumor cells proliferation.1.3 The experiment results showed that BAI1,p53,expression increased with the decylubiquinone treatment.2 Study of the LBP effects on inhibiting tumor angiogenesis2.1 The in vitro experiments results showed that LPS can inhibit tumor angiogenesis and suppress tumor growth.2.2 LBP didnot inhibited endothelial cell and tumor cells proliferation,however,LPS could inhibit angiogenesis.