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端粒酶抑制剂与丝裂霉素联合应用对膀胱癌的作用研究

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

  • 摘要: 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。

     

    Abstract: 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 telomerase and 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.

     

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