端粒酶反义寡核苷酸对二甲肼诱导大鼠大肠癌的预防作用

Prevention of antisense oligonucleotide of telomerase against colon cancer in rats induced by dimethylhydrazine

目的 :探讨端粒酶反义寡核苷酸对二甲肼诱导大鼠大肠癌的预防作用。方法 :用 1,2 二甲肼 ( 1,2 DMH)诱导SD大鼠肠癌发生的模型 ,观察端粒酶反义寡核苷酸对端粒酶活性及二甲肼诱癌率的影响。结果 :本研究使用二甲肼成功地诱导了大鼠大肠癌发生模型 ,阴性对照组未见肿瘤发生 ,阳性诱癌组诱癌率为 5 7 6 9% ,反义寡核苷酸保护组诱癌率为 2 6 92 % ,明显低于阳性诱癌组 (P <0 0 1) ;同时反义寡核苷酸保护组端粒酶活性低于阳性诱癌组 (P <0 0 5 )。结论 :端粒酶反义寡核苷酸在体内能抑制端粒酶活性 ,对DMH诱导的肠癌有预防作用 。

Objective:To reveal the possibility of antisense oligonucleotide of telomerase used as an effective agent for tumor prevention. Methods:The colon carcinogenesis model induced by 1,2 dimethylhydrazine (1,2 DMH) was used to observe the effect of antisense oligonucleotide of telomerase on the inhibition of telomerase activity and the rate of colon carcinagenesis induced by 1,2 DMH. Results:The colon carcinogenesis model was successfully established in this experiment. As a result,the negative control group develop tumor. The cancer inducing rate of positive control group is 57 69%,while that of the oligonucleotide protecting group is 26 92%. The difference between the two groups is statistically significant (P< 0 01). The activity of telomerase in the olgonucleotide protecting group is lower than that of the positive group starting from 10th week of DMH administration (P< 0 05). Conclusion:The antisense oligoncleotide of telomerase can inhibit the activity of telomerase and increale the protection rat of induced colon cancer in vivo. It might be an effective agent for the prevention and treatment of colon cancer.