Endostatin抑制小鼠膀胱癌的作用机理研究

Mechanism of endostatin inhibiting growth of mouse bladder cancer

目的 探讨endostatin抑制膀胱癌生长的作用机理。 方法 体外培养小鼠膀胱移行细胞癌T739细胞 ,以endostatin 10 μg/ml处理 ,观察细胞增殖、凋亡情况 ;endostatin 2 0mg·kg-1·d-1皮下注射T739膀胱癌荷瘤小鼠 ,观察肿瘤细胞增殖、凋亡指数及Fas与Bcl 2在肿瘤细胞中的表达。 结果 体外实验显示 ,对照组及endostatin组T739细胞增殖指数分别为 (5 8.3± 9.3) %、(5 9.4± 8.6 ) % ,凋亡指数分别为 (7.2± 1.1) %、(7.5± 1.0 ) % ,差异均无显著性意义 (P >0 .0 5 ) ;动物实验显示 ,对照组及endostatin组肿瘤细胞增殖指数分别为 (5 9.1± 6 .7) %、(5 8.6± 6 .3) % ,差异无显著性意义 (P >0 .0 5 ) ;对照组凋亡指数为 (1.9± 0 .4 ) % ,治疗组为 (9.7± 0 .9) % ,差异有显著性意义 (P <0 .0 1) ;endo statin组肿瘤细胞Fas表达明显增加 ,对照组及治疗组肿瘤细胞均无明显Bcl 2表达。 结论 endo statin可能通过抑制血管形成导致组织缺氧 ,上调Fas表达诱导肿瘤细胞凋亡 ,从而抑制小鼠膀胱癌生长。

Objective To investigate the mechanism of endostatin inhibiting the growth of mouse T739 bladder cancer. Methods Treated with endostatin 10 μg/ml,T739 cells were evaluated by proliferating cell nuclear antigen(PCNA) and TUNEL in vitro.T739 cell-bearing mice were administrated with endostatin 20 mg·kg -1 ·d -1 .12 days later,histological sections of tumors were analyzed for PCNA and TUNEL,immunohistochemical staining of Fas and Bcl-2 were monitored by confocal laser scanning microscope. Results In vitro,the proliferation index (PI) of T739 cells was(58.3±9.3)% in group of control,(59.4±8.6)% in group of endostatin( P >0.05), and the apoptotic index (AI) was (7.2±1.1)% in group of control,(7.5±1.0)% in group of endostatin( P >0.05).In vivo,the PI of mouse tumor cells was(58.6±6.3)% in group of endostatin,(59.1±6.7)% in the control( P >0.05).The AI of tumor cells was(9.7±0.9)% in mice treated with endostatin compared to that (1.9±0.4)% in the group of control ( P <0.01).The expression of Fas in tumor cell membrane increased in mice treated with endostatin.There was no difference of Bcl-2 expression between the tumor cells in mice treated with endostatin and that in the control. Conclusions Inhibiting angiogenesis of tumor,endostatin may induce ischemia and hypoxygen in tumor tissue,which result in Fas expression and signaling apoptotic cell death,thus endostatin can suppress growth of bladder cancer in mice.