【摘要】 目的：探讨端粒酶抑制剂对动物在体肿瘤的治疗价值及端粒酶抑制剂是否增加放射治疗的疗效。方法：采用正交实验设计，应用端粒酶抑制剂 [齐多夫啶 (azidothymidine， AZT)： 300 mg· kg－ 1· d－ 1；拉米夫啶 (lamivudine)： 150 mg· kg－ 1· d－ 1]联合放射 (每周照射 5次，每次 DT 2 Gy，总量 10 Gy/周 )治疗 BALB/c小鼠移植性乳腺癌 (MA782)，观察其对肿瘤体积缩小和肿瘤内端粒酶表达的影响。肿瘤体积用游标电子数显卡尺测量计算，并采用 PCR ELISA方法检测端粒酶活性。结果：本研究结果表明，未治疗、单用 lamivudine治疗的小鼠肿瘤体积分别增大 2.7268、 2.5130倍，表明单纯使用 lamivudine作用不明显 (P >0.05)；而经 AZT、放疗、 AZT加放疗治疗的小鼠肿瘤体积分别缩小 20.72％、 47.43％、 85.19％，提示 AZT、放疗均能使肿瘤体积缩小 (P< 0.05)，并且 AZT与放疗的联合作用明显优于两者的单独作用 (P< 0.05)。而肿瘤端粒酶活性检测表明，未处理，以及经 AZT、 lamivudine、放疗、 AZT加放疗、 AZT加 lamivudine加放疗处理的肿瘤端粒酶 A值分别为 0.817、 0.453、 0.760、 0.480、 0.340、 0.166，显示 AZT、放疗、 lamivudine均有减少肿瘤端粒酶活性的作用 ( P< 0.05)，且 AZT与放疗有相加作更多还原

【Abstract】 Objective： This study was designed to evaluate the treatment value of telomerase inhibitors for animal tumor in vivo and investigate radiosensitive effects of telomerase inhibitors. Methods： With orthogonal experiment design, the telomerase inhibitors(azidothymidine AZT 300 mg· kg－ 1· d－ 1, lamivudine 150 mg· kg－ 1· d－ 1)and radiotherapy (RT, 10 gray in a week, 2 gray/Fx, 5 Fx/wk) were used to treat breast cancers (MA782)xenograft in BALB/c mice for evaluating their influence on tumor size and telomerase expression. The tumor size was measured with a digital vernier scale. Telomerase activity was examined by a PCR-based telomeric repeat amplification protocol (TRAP) coupled with ELISA. Results： The tumor size of mice increased 2.7268 times in untreated and 2.5130 times in lamivudine-administrated, which indicated lamivudine having no obvious effect on tumor volume (P >0.05)； AZT, RT, and AZT combined with RT reduced tumor volume of 20.70％ , 47.43％ , and 85.19％ , respectively, and combined model(AZT＋ RT) was more effective than others used alone(P< 0.05); The A value of tumor telomerase was untreated,0.817; AZT,0.453; lamivudine,0.760; RT,0.480; AZT 0.340 combined with RT； and AZT plus lamivudine plus RT,0.166 ; which suggested that AZT, RT and lamivudine could decrease the activity of tumor telomerase (P< 0.05), and furthermore, AZT combined with RT have an additive effect (P< 0.05). Conclusion： Both AZT and radiotherapy are effective to treat murine breast cancer through decreasing telomerase activity and reducing tumor size. AZT can increase the radiation sensitivity for murine breast cancer MA782. Telomerase is a new target for anticancer treatment.更多还原