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 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.