端粒酶抑制剂与丝裂霉素联合应用对膀胱癌的作用研究

 目的 探讨端粒酶抑制剂与化疗药物联合应用对荷瘤小鼠肿瘤生长的影响。方法 应用端粒酶抑制剂齐夫多啶（AZT）联合化疗药物丝裂霉素（MMC）治疗小鼠移植性膀胱癌（T24），观察其对抑瘤率、肿瘤端粒酶的表达及肿瘤细胞凋亡的影响。结果 AZT、MMC、MMC＋AZT抑瘤率分别为12．1％、29．6％和43．6％，TUNEL法检测肿瘤细胞凋亡指数分别为（20．23±0．89）％、（8．04±0．12）％和（24．09±1．81）％。肿瘤端粒酶活性检测显示各组端粒酶阳性率分别为36．5％、43．6％和11．8％，与对照组比较，AZT、MMC均有减少肿瘤端粒酶活性的作用（P〈0．05）。AZT与MMC联用明显优于两者单独应用（P〈0．05）。结论 MMC及AZT均能抑制小鼠膀胱癌T24细胞的生长及降低其端粒酶活性、诱导细胞凋亡，二者联用有相加作用。

Effect of Telomerase Inhibitor Combined with Mitomycin on Bladder Cancer Xenograft in Mice

Objective 　To evaluate t reatment value of telomerase inhibitor (azidothymidine ,AZT) together with mitomycin (MMC) for animal tumor in vivo. Methods 　AZT and chemotherapy agent (MMC) were ued to t reat bladder cancer ( T24) xenograf t in BALB/ C mice. Their influence on tumor weight ,telomerase expression and apoptotic indices (AI) were evaluated. Telomerase activity was examined by a PCR-based telomeric repeat amplification protoco ( TRAP) coupled with EL ISA. AI were examined by terminal eoxynueleotidyl t ransferase-mediated deoxyuridime triphosphate fluorescence nick end labeling (TUNEL) method. Morphological changes were observed under microscopy. Results 　Tumor weight was reduced to 12. 1 % ,29. 6 % and 43. 6 % in AZT ,MMC and AZT combined with MMC respectively. AI was (20. 23 ±0. 89) % , (8. 04 ±0. 12) % and (24. 09 ±1. 81) % respectively ,which indicated that both AZT and MMC could induce apoptosis ,and AZT combined with MMC was superior to AZT or MMC used alone ( P < 0. 05) . The positive rates of telomerase activity were 36. 5 % in AZT , 43. 6 % in MMC ,and 11. 8 % in AZT + MC ,suggesting both AZT and MMC could decrease the activity of tumor telomeraseand AZT combined with MMC had an additive effect ( P < 0. 05) . Conclusion 　Both AZT and MMC are effective to t reat bladder cancer T24 through decreasing telomerase activity and reducing tumor weight ,enhancing apoptosis. AZT can increase chemotherapy sensitivity for T24.