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。
Objective To evaluate treatment value of telomerase inhibitor （azidothymidine, AZT） together with mitomycin（MMC） for animal tumor in vivo. Methods AZT and chemotherapy agent （MMC） were used to treat bladder cancer （T24） xenograft in BALB/C mice. Their influence on tumor weight, telomerase expression and apoptotic indices （AI） were evaluated. Telomerase activity was examined by a PCRbased telomeric repeat amplification protoco （TRAP） coupled with ELISA. AI were examined by terminal deoxynueleotidyl transferase-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 ＋ MMC, 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 treat bladder cancer T24 through decreasing telomerase activity and reducing tumor weight, enhancing apoptosis. AZT can increase chemotherapy sensitivity for T24.
出处
《肿瘤防治研究》
CAS
CSCD
北大核心
2005年第9期574-576,共3页
Cancer Research on Prevention and Treatment
关键词
端粒酶
膀胱癌
凋亡
Telomerase
Bladder cancer
Apoptosis
