Mechanism Of Angiogenin Negatively Regulates BFGF And Influence Of Angiogenin On Tumor Cells

Tumor vessel is the basis of tumor growth and tumor metastasis. Angiogenin is a14-kDa angiogenic protein originally isolated from the conditioned medium of HT-29human colon adenocarcinoma cells based on its angiogenic activity. Basic fibroblastgrowth factor(bFGF) which is widespread in bodies can promote neovascularity, andthe it is overexpressed in many tumor tissues. Angiogenin and bFGF are two potentand representative angiogenesis factors which play an important role in tumorangiogenesis and development. Many studies have mainly focused on how it inducesangiogenesis, in this study, we report that angiogenin negatively regulates bFGFexpression in HeLa cells and the effects of angiogenin on tumor growth, migration,and invasion were also investigated in this thesis.The results showed that bFGF promoter activity was inhibited by angiogenin.Angiogenin undergoes nuclear translocation and an angiogenin binding site(CTCTCTCT) on bFGF promoter has been identified. Moreover, MTT, FlowCytometry, soft agar assay and Transwell were used to detect the effect of angiogeninon tumor growth, migration, and invasion and the results suggestted that angiogeninhas a directly effect on tumor growth, migration and invasion of A375 cells. We alsofound that neamine positively inhibited the proliferation, migration and invasion ofA375 cells.In conclusion, we demonstrated that the mechanism of angiogenin negativelyregulates bFGF is a cumulative result of many factors. On the one hand, angiogenincan bind and promoter region of bFGF and inhibit its transcriptional as a transcriptionfactor, On the other hand, there may be a negative feedback regulation of angiogeninand bFGF in the cancer cells. To investigate the mechanisms of the interaction betweenthe two factors has an important significance for targeted therapy of tumorangiogenesis.In this study we also found the promotion of angiogenin on tumor growth,migration and invasion and the inhibition of neamine on tumor, these results provide atheoretical basis for the development of new anticancer drugs.