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RNAi 沉默人端粒酶逆转录酶基因抑制 A549 肺腺癌细胞的体内外生长。

Silencing of the human TERT gene by RNAi inhibits A549 lung adenocarcinoma cell growth in vitro and in vivo.

机构信息

Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha 410008, PR China.

出版信息

Oncol Rep. 2011 Oct;26(4):1019-27. doi: 10.3892/or.2011.1383. Epub 2011 Jul 8.

Abstract

Human telomerase reverse transcriptase (hTERT) is the catalytic subunit and the activity determinant factor of the telomerase enzyme which maintains the length of human chromosomes. In recent years it has become an attractive molecular target for cancer gene therapy. In the present study, we show that hTERT siRNA effectively suppressed the expression of hTERT mRNA and hTERT protein levels, reduced telomerase activity, and induced apoptosis of A549 lung adenocarcinoma cells (P<0.05). In vivo, tumors treated with the hTERT siRNA were of reduced sizes, indicating that the hTERT siRNA also reduced the tumorigenic potential of lung adenocarcinoma cells (P<0.05). These results demonstrate that hTERT siRNA can cause effective suppression of telomerase and lead to apoptosis in A549 lung adenocarcinoma cells. hTERT siRNA may, therefore, be a strong candidate for highly selective therapy for chemoprevention and treatment of lung adenocarcinoma.

摘要

人端粒酶逆转录酶(hTERT)是端粒酶的催化亚基和活性决定因素,端粒酶维持人类染色体的长度。近年来,它已成为癌症基因治疗的一个有吸引力的分子靶标。在本研究中,我们表明 hTERT siRNA 可有效抑制 hTERT mRNA 和 hTERT 蛋白水平的表达,降低端粒酶活性,并诱导 A549 肺腺癌细胞凋亡(P<0.05)。在体内,用 hTERT siRNA 处理的肿瘤体积减小,表明 hTERT siRNA 也降低了肺腺癌细胞的致瘤潜能(P<0.05)。这些结果表明,hTERT siRNA 可有效抑制端粒酶并导致 A549 肺腺癌细胞凋亡。因此,hTERT siRNA 可能是用于肺腺癌化学预防和治疗的高度选择性治疗的有力候选者。

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