Effects of creatine phosphate on angiogenesis in mice with transplanted S180 sarcoma and its possible mechanism

HAN Wenfeng; WEI Suju; ZHENG Yazhen

doi:10.3969/j.issn.1002-7386.2017.14.002

Abstract：Objective To investigate the effects of creatine phosphate ( Cp ) on angiogenesis in mice with transplanted S180 sarcoma, and to explore its related action mechanism. Methods The animal models with S180 sarcoma were established in Kunming mice. The 60 mice were randomly divided into four groups:control group,low-dose group ( Cp 200mg/kg),middle-dose group ( Cp 400mg/kg), high-dose group ( Cp 800mg/kg). The changes of transplanted tumors weight were observed, moreover, the expression levels of ( matrix metalloproteinase-2 ( MMP-2 ) and tissue inhibitors of metalloproteinases ( TIMP-2 ) protein in transplanted sarcoma tissues were detected by flow cytometry, and the microvessel density (MVD) of tumors was detected by immunohistochemistry (IHC),besides the expression levels of VEGF and bFGF mRNA in transplanted tumor were detected by RT-PCR. Results There were no significant differences in transplantation tumor weight, the expression levels of VEGF, bFGFmRNA, MMP-2, TIMP-2 among control group, low-dose group and middle-dose group (P>0. 05). However the transplantation tumor weight in high-does group was significantly decreased,as compared with those in control group, low-dose group and middle-dose group,moreover MVD was obviously decreased,and the expression levels of VEGF, bFGFmRNA and MMP-2 protein were significantly decreased, however, the expression levels of TIMP-2 protein were significantly increased (P <0. 01). Conclusion The low-dose and middle-dose Cp has no obvious inhibitory effects on angiogenesis in mice with transplanted S180 sarcoma, however high-dose Cp has obvious inhibitory effects on angiogenesis in mice with transplanted S180 sarcoma, and its action mechanism might be correlated to down-regulation of expression levels of MMP-2,VEGF,bFGF and up-regulation of TIMP-2 expression.