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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 effect of intratumor injection of telomerase inhibitor AZT on implanted hepatocellular carcinoma (HCC) in rats and explore the possibility of using telomerase inhibitor in the treatment of malignant tumor. Methods: SD male adult rats were made into the model of implanted hepatocellular carcinoma (HCC) by injecting the B-supercanced cancer cell suspension and passaged in Wistar male rats. The liver cancer model rats were selected and divided into two groups at random. The AZT-treated rats (n = 21) underwent direct intratumoral injection of AZT, the control rats (n = 21) received intratumoral injection of normal saline, The tumor volume was measured respectively. The telomerase activity was detected by TRAP ELISA. MGPMY staining was used to observe the apoptosis and calculate the apoptosis rate. Results: The telomerase activity in AZT group was significantly lower than that in control group on day 6 after treatment (0.426 ± 0.162 and 0.767 ± 0.102, respectively, both P <0.05), while the apoptosis rate in AZT group was significantly higher [(4 447.870 ± 28.107) mm3, (759.885 ± 22.154) mm3, P (P <0.05)] in the AZT group (12.439 ± 0.802)% vs 3.903 ± 0.182% <0.05]. Conclusion: AZT can effectively reduce telomerase activity, induce apoptosis and reduce tumor growth in tumor-bearing rats. Telomerase inhibitor is a potential therapeutic approach for clinical treatment.