TNP-470与阿霉素联合使用治疗小鼠膀胱癌

目的观察血管形成抑制剂TNF-470与化疗药物阿霉素联合应用抑制小鼠膀胱癌的协同作用.方法分别予TNP-470、阿霉素、TNP-470 阿霉素治疗TN39膀胱癌荷瘤小鼠,观察肿瘤生长及血管形成、细胞凋亡情况.结果治疗后12 d,TNP-470、阿霉素及TNP-470 阿霉素治疗组抑瘤率分别为46.3%、21.4%及56.5%,TNP-470组微血管密度明显减少、凋亡指数增多,阿霉素组凋亡指数增多,TNP-470 阿霉素组凋亡指数进一步增加.结论TNP-470与阿霉素治疗小鼠膀胱肿瘤,有明显的抗肿瘤协同作用,其机理可能是通过抑制血管形成及化疗药物细胞毒性作用而促使肿瘤细胞凋亡进一步增加.

Combined effects of TNP- 470 with adriamycin on mouse model of bladder cancer

Objective: To investigate the combined effects of angiogenesis inhibitor TNP-470 with adriamycin on tumor growth and neovascularization in mouse model with subcutaneously implanted bladder cancer. Methods:Treated with TNP-470 with or without adriamycin for 12 days, tumor growth and the states of angiogenesis, cell proliferation and apoptosis of tumor were evaluated immunohistochemically in mouse model with subcutaneously implanted bladder cancer. Results: TNP-470, adriamycin and TNP-470 plus adriamycin reduced tumor volume with 46.3%, 21.4% and 56.5%, respectively. We noted a significantly decreased microvessel density (MVD) in mouse bladder cancer treated by TNP-470, and a significantly increased apoptotic index when treated by TNP-470 and adriamycin. In TNP-470 plus adriamycin-treated mouse, further increasing apoptotic index was observed in tumor. There was no significant different proliferation index in these groups. Conclusions: Combination of TNP-470 with adriamycin resulted in increasing antitumor activity and efficacy on mouse bladder cancer. The combined therapy of TNP-470 with adriamycin may act through both the inhibition of angiogenesis and induction of apoptosis.