【摘要】 目的　探讨端锚聚合酶 1(tankyrase 1,TANK1)反义寡核苷酸对人肺癌细胞的影响 ,为肺癌治疗的靶向研究探索新途径。方法　合成TANK1正义寡核苷酸 (TANK1 SODN)、反义寡核苷酸(TANK1 ASODN) ,待人肺癌细胞株CALU在裸鼠蹊部皮下接种成瘤后 ,将成瘤裸鼠随机分成 3组 :对照组 4只 (每天上午于瘤体内多位点注射生理盐水 2 0 0 μl/只 ) ,正义组 (每天同法注射含TANK SODN10 0 μg的生理盐水 2 0 0 μl/只 )和反义组 (每天同法注射含TANK ASODN 10 0 μg的生理盐水 2 0 0 μl/只 )各 5只 ,观察肿瘤的生长情况及组织学改变。用链霉亲和素 生物素 酶复合物 (SABC)法检测肿瘤细胞Ki6 7及端粒酶反转录酶 (hTERT)的阳性表达率。结果　在裸鼠成瘤部位连续注射相应液体 16d后 ,反义组移植瘤体积为 (1 4 6± 0 70 )cm3 ,明显小于对照组的 (3 2 9± 0 4 7)cm3 及正义组的 (3 14±0 70 )cm3 ,差异有显著性 (P均 <0 0 1) ;肿瘤细胞Ki6 7标记指数及hTERT细胞阳性率均明显低于对照组及正义组 (P均 <0 0 1)。结论　人肺癌细胞株端粒酶呈高度表达 ,TANK1 ASODN可降低瘤细胞端粒酶活性 ,抑制肺癌细胞增殖更多还原

【Abstract】 Objective To observe the suppressing effect of antisense oligodeoxynucleotides of tankyrase 1 (TANK1-ASODN) on murine tumor growth following intratumoral injection, and to explore its potential use in clinical treatment of lung cancer. Methods After human lung cancer cells CALU had been inoculated subcutaneously to BALB/c nude mice and grew to tumor nodules, these mice were distributed randomly into three groups: four in the saline group, five in the TANK1-ASODN group, and another five in the sense oligodeoxynucleotides of tankyrase(TANK1-SODN) group. Multiple direct intratumoral injections of TANK1-ASODN, TANK1-SODN or saline were given into the tumor nodules, respectively. The tumor growth and the histopathological characteristics were observed and the expression of ki67 and telomerase hTERT in tumor cells were measured by SABC immunohistrochemical method . Results After 16 days of continuous injection, the tumor volume of the TANK1-ASODN group was significantly smaller than that of the TANK1-SODN(P<0.01) and saline-treated groups(P<0.01); tumor cell degeneration and necrosis were observed in mice treated with TANK1-ASODN. Moreover, a statistically significant decrease in Ki67 labeling index(P<0.01) and the positive expression ratio of telomerase hTERT(P<0.01) was observed in the TANK1-ASODN group. Conclusions Human lung tumor cell lines express high telomerase activity.TANK1-ASODN can inhibit the activity of telomerase and suppress the proliferation of tumor cells.更多还原