Neamine is preferential as an anti-prostate cancer reagent by inhibiting cell proliferation and angiogenesis, with lower toxicity than cis-platinum

摘要

Hormone therapy is the most commonly used treatment for prostate cancer, but for androgen-independent cancer, few effective treatment methods are available. Therefore, the requirement to develop novel and effective anti-prostate cancer drugs is extremely urgent. Angiogenin has been suggested as a molecular target for prostate cancer treatment; its overexpression contributes to androgen-dependent prostate cancer growth and castration-resistant growth of androgen-independent prostate cancer. The aim of the present study was to investigate whether neamine, a low toxicity angiogenin nuclear translocation inhibitor, has preferential anti-prostate cancer activity compared with cis-platinum (DDP) and the mechanisms involved. Immunofluorescence and MTT assays were used to observe the effect of neamine on the nuclear translocation of angiogenin and cell proliferation, and a PC-3 cell transplanted tumor model was used to investigate the in vivo activity of neamine and DDP. Immunohistochemistry was performed to observe the expression of angiogenin, cluster of differentiation (CD)31 and Ki-67. It was found that neamine blocked nuclear translocation of angiogenin effectively and inhibited angiogenin-induced human umbilical vein endothelial cell and PC-3 cell proliferation in a dose-dependent manner. Neamine exerted a comparative antitumor effect, but lower toxicity (weight loss), in the PC-3 xenograft models treated with DDP. Neamine consistently reduced the expression of angiogenin and CD31 significantly, but no difference was found in Ki-67 expression compared with DDP. These data suggested that neamine may be a promising agent for prostate cancer treatment.