瘤内注射端粒酶抑制剂AZT对大鼠种植性肝癌的影响

Effects of intratumoral injection of telomerase inhibitor AZT on implanted liver cancer in rats

目的:观察瘤内注射端粒酶抑制剂AZT对大鼠种植性肝癌的影响,探讨端粒酶抑制剂治疗恶性肿瘤的可能性。方法:将SD雄性成年大鼠采用B超引导下癌细胞悬液注入法制作大鼠种植性肝癌模型,并用Wistar雄性大鼠传代。选取肝肿瘤大小接近的肝癌模型大鼠随机分为2组,AZT治疗组大鼠(n=21)行直视下瘤内注射AZT,对照组大鼠(n=21)瘤内注射生理盐水,分别测量肿瘤体积、采用TRAPELISA法测定肿瘤组织端粒酶活性、MGPMY组合染色观察细胞凋亡并计算细胞凋亡率。结果:处理后第6天AZT组肿瘤组织端粒酶活性明显低于对照组(分别为0.426±0.162、0.767±0.102,二者比较P<0.05),而肿瘤细胞调亡率AZT组明显升高[AZT组(12.439±0.802)%,对照组(3.903±0.182)%,P<0.05],体积比较AZT组明显小于对照组[分别为(449.870±28.107)mm3、(759.885±22.154)mm3,P<0.05]。结论:AZT能有效降低荷瘤大鼠肿瘤组织的端粒酶活性、诱导细胞凋亡、减缓肿瘤生长,端粒酶抑制剂治疗恶性肿瘤是一种可能应用于临床的方法。

Objective：To observe the effects of intratumora[ injection of telomerase inhibitor （azidothymidine, AZT） on implanted liver cancer in rats so as to assess the therapeutic value of AZT for malignant tumor. Methods： laver cancer models were developed with male adult SD rats by injecting cancerous suspension （Walker-256） into the rat liver under the guidance of B ultrasound. Male Wistar rats were used for tumor passaging. Forty-two tumor model rats were equally randomized into AZT group and control group： intratumoral injection of AZT was given to AZT group and equal volume of normal saline was given to control group. The telomerase activity,apoptotic indices（AI） and tumor volumes were determined in 2 groups. Telomerase activity was examined by telomeric repeat amplification proctocol coupled with ELISA （TRAP-ELISA）. Morphological changes of apoptotic tumor cells were observed with MG-P-MY staining and AI was calculated. Tumor volumes were measured 6 d after treatment in 2 groups. Results： The tumor volume was significantly reduced in AZT group compared with that in control group 6 d after treatment （[449. 870±28. 107] mm^3 vs [759. 885±22. 154] mm^3 , P〈0.05） ; the telomerase activity was significantly lower in AZT group compared with that in control group（0. 426±0. 162 vs 0. 767±0.10,P〈0.05） ; and the AI was significantly higher in AZT group compared with that in control group （ [12. 439±0. 8021] vs [3. 903±0. 1821], P〈0.05） . Conclusion： AZT can decrease telomerase activity, induce tumor cell apoptosis and slow down tumor growth, indicating that AZT might be a feasible treatment for malignant tumors.