端粒酶RNA反义寡核苷酸对人绒毛膜癌裸鼠移植瘤的生长抑制作用

Telomerase RNA antisense oligonucleotides inhibit growth of human choriocarcinoma xenograft in nude mice

目的 探讨端粒酶RNA反义寡聚核苷酸 (anti hTR)对绒癌的治疗作用。方法 采用绒癌JAR细胞移植裸鼠成瘤 ,行anti hTR的低浓度和高浓度治疗 ,并设立生理盐水组、随机序列组及药物放线菌素D (Act D)对照组 ,动态观察并测定肿瘤的生长。采用TRAP ELISA方法测定端粒酶活性。采用Westernblot法测定hTERT蛋白的表达。结果 anti hTR低浓度组、高浓度组和药物Act D组的抑瘤率分别为 76 .6 %、93.8%和 85 .4 % ,三组对肿瘤生长的抑制 ,与随机序列组和生理盐水组相比 ,差异均有统计学意义 ,而三组之间差异无统计学意义。三组的端粒酶活性及hTERT蛋白表达下降 ,较随机序列组和生理盐水组相比 ,差异均有统计学意义 ,而三组之间差异无统计学意义。结论 anti hTR能够抑制绒癌移植瘤的生长 ,可能成为肿瘤治疗的新方法。

Objective To study the inhibitory effect of antisense oligonucleotides against telomerase RNA on the growth of human choriocarcinoma transplant in nude mice. Methods Choriocarcinoma xenografts were established by transplanting JAR cells subcutaneously to female nude mice, and were treated with high and low doses of antisense oligonucleotides. Control groups were treated with NS, random sequence and actinomycin D (Act D). Tumor growth was monitored once every other day. Telomerase relative activity was assayed by TRAP ELISA. Western blotting was used to detect expression of hTERT. Results Low and high doses antisense oligonucleotides, and Act D inhibited tumor growth by 76.6%, 93.8% and 85.4% respectively, which were significantly different when compared with random sequence and NS groups. Expression of telomerase relative activity and hTERT were decreased as well. But the differences among the first three groups had no significance. Conclusion Telomerase RNA antisense oligonucleutide inhibits growth of human choriocarcinoma xenografts in nude mice. It may be a novel approach to the treatment of choriocarcinoma.