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端粒酶抑制剂与阿霉素联合应用治疗小鼠膀胱癌

Effect of telomerase inhibitor combined with adriamycin on mouse model of bladder cancer
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摘要 目的观察端粒酶抑制剂与化疗药物阿霉素联用抑制小鼠膀胱癌的协同作用。方法AZT(端粒酶抑制剂齐夫多啶)4.5mg、阿霉素0.1mg、AZT4.5mg+阿霉素0.1mg分组治疗T24膀胱癌荷瘤小鼠,观察肿瘤生长、细胞凋亡情况。结果治疗后15d,AZT、阿霉素、AZT+阿霉素各治疗组抑瘤率分别为35.6%、18.5%和43.2%。TUNEL法检测各组肿瘤细胞凋亡指数为(18.16±0.78)、(9.23±0.22)和(25.15±1.65)。肿瘤端粒酶活性检测示各组端粒酶阳性率分别为24.5%、47.2%和12.3%,AZT、阿霉素均有减少肿瘤端粒酶活性的作用,且联用效果明显优于两者单独应用(P〈0.05)。结论AZT及阿霉素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,两者联用有相加作用。 Objective To investigate the synergic effects of telomerase inhibitor (AZT) combined with adriamycin for animal bladder cancer in vivo. Methods Telomerase inhibitor (AZT) 4.5 mg and adriamycin 0.1 mg were used to treat bladder cancer xenograft in BALB/C mice. Their influence on tumor weight, telomerase expression and apoptotic index (AI) were evaluated. Telomerase activity was examined by a PCR based telomeric repeat amplification pmtoco (TRAP) coupled with ELISA. AI was 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 35.6% ,18.5% and 43.2% in AZT,adriamycin and AZT combined with adriamycin groups respectively, and AI was ( 18.16 ± 0.78 ), (9.23 ± 0.22) and (25.15 ± 1.65 ) respectively, which indicated that both AZT and adriamycin could induce apoptosis, and AZT combined with adriamycin was superior to AZT or adriamycin used alone ( P 〈 0.05 ). The positive rates of telomerase activity was 24.5,47.2 and 12.3 in AZT, adriamycin and AZT combined with adriamycin groups respectively,suggesting both AZT and adriamycin could decrease the activity of tumor telomerase and AZT combined with adriamycin had an additive effect ( P 〈 0.05 ). Conclusion Both AZT and adriamycin are effective to treat bladder cancer T24 through decreasing telomerase activity and reducing tumor weight, enhancing apoptosis. Combined use of them has a synergic effect on bladder cancer.
出处 《中华实验外科杂志》 CAS CSCD 北大核心 2008年第4期490-491,共2页 Chinese Journal of Experimental Surgery
关键词 膀胱癌 端粒酶 脱噬作用 阿霉素 Bladder carcinoma Telomerase Apoptosis Adriamycin
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