Bajpai Arun K, Park Jeong-Hoh, Moon Ik-Jae, Kang Hyungu, Lee Yun-Han, Doh Kyung-Oh, Suh Seong-Il, Chang Byeong-Churl, Park Jong-Gu
WelGENE Inc. 71B-4L, Hightech sector 2, Sungseo Industrial Park III, Dalseogu, Daegu 704-230, Republic of Korea.
Oncogene. 2005 Sep 29;24(43):6492-501. doi: 10.1038/sj.onc.1208731.
Ribbon antisense (RiAS) to the hTR RNA, a component of the telomerase complex, was employed to inhibit telomerase activity and cancer cell growth. The antisense molecule, hTR-RiAS, combined with enhanced cellular uptake was shown to effectively inhibit telomerase activity and cause rapid cell death in various cancer cell lines. When cancer cells were treated with hTR-RiAS, the level of hTR RNA was reduced by more than 90% accompanied with reduction in telomerase activity. When checked for cancer cell viability, cancer cell lines treated with hTR-RiAS using DNA+Peptide+Lipid complex showed 70-80% growth inhibition in 3 days. The reduced cell viability was due to apoptosis as the percentage of cells exhibiting the sub-G0 arrest and DNA fragmentation increased after antisense treatment. Further, when subcutaneous tumors of a colon cancer cell line (SW480) were treated intratumorally with hTR-RiAS, tumor growth was markedly suppressed with almost total ablation of hTR RNA in the tumor tissue. Cells in the tumor tissue were also found to undergo apoptosis after hTR-RiAS treatment. These results suggest that hTR-RiAS is an effective anticancer reagent, with a potential for broad efficacy to diverse malignant tumors.
端粒酶复合物的一个组成部分hTR RNA的带状反义核酸（RiAS）被用于抑制端粒酶活性和癌细胞生长。反义分子hTR-RiAS与增强的细胞摄取相结合，被证明能有效抑制端粒酶活性并在各种癌细胞系中导致快速细胞死亡。当用hTR-RiAS处理癌细胞时，hTR RNA水平降低了90%以上，同时端粒酶活性也降低。在检测癌细胞活力时，使用DNA+肽+脂质复合物处理hTR-RiAS的癌细胞系在3天内显示出70-80%的生长抑制。细胞活力降低是由于凋亡，因为反义处理后显示亚G0期停滞和DNA片段化的细胞百分比增加。此外，当用hTR-RiAS对结肠癌细胞系（SW480）的皮下肿瘤进行瘤内治疗时，肿瘤生长明显受到抑制，肿瘤组织中的hTR RNA几乎完全消失。在hTR-RiAS处理后，还发现肿瘤组织中的细胞发生凋亡。这些结果表明，hTR-RiAS是一种有效的抗癌试剂，对多种恶性肿瘤具有广泛疗效的潜力。
