Shi Ying-Ai, Zhao Qiang, Zhang Li-Hong, Du Wei, Wang Xue-Yao, He Xu, Wu Shan, Li Yu-Lin
Key Laboratory of Pathobiology, Ministry of Education, School of Basic Medical Sciences, Jilin University, Changchun 130021, P.R. China.
Department of Pediatric Surgery, The First Hospital, Jilin University, Changchun 130021, P.R. China.
Int J Oncol. 2014 Sep;45(3):1216-24. doi: 10.3892/ijo.2014.2493. Epub 2014 Jun 11.
Human telomerase reverse transcriptase (hTERT) is the catalytic component of telomerase that facilitates tumor cell invasion and proliferation. It has been reported that telomerase and hTERT are significantly upregulated in majority of cancers including cervical cancer, thus, downregulation of hTERT is a promising target in malignant tumor treatment. We established a short interfering RNA (siRNA) targeting hTERT, and transfected it into HeLa cells (a cervical cancer cell line) to investi-gate the effect of cell proliferation, apoptosis, migration and invasion in cervical cancer cells. The results showed that siRNA targeting hTERT could effectively knock down hTERT expression, remarkably suppress telomerase activity, cell proliferation, migration and invasion, and induced cell apoptosis of cervical cancers cells in vitro. In addition, we evaluated whether siRNA targeting hTERT affects tumor growth in nude mice, and found that it dramatically inhibited tumorigenesis and growth of mice injected with siRNA targeting hTERT. Furthermore, we also found that knockdown of hTERT was able to significantly suppress constitutive phosphorylation of Akt, PI3K, which might imply that reduction of hTERT inhibited tumor growth via the PI3K/Akt signaling pathway to some extent. These results suggest that the suppression of hTERT expression by siRNA inhibits cervical cancer cell growth in vitro and in vivo, and may provide a novel target for anticancer gene therapy.
人端粒酶逆转录酶（hTERT）是端粒酶的催化成分，可促进肿瘤细胞的侵袭和增殖。据报道，在包括宫颈癌在内的大多数癌症中，端粒酶和hTERT均显著上调，因此，下调hTERT是恶性肿瘤治疗中一个有前景的靶点。我们构建了靶向hTERT的小干扰RNA（siRNA），并将其转染至HeLa细胞（一种宫颈癌细胞系）中，以研究其对宫颈癌细胞增殖、凋亡、迁移和侵袭的影响。结果表明，靶向hTERT的siRNA可有效敲低hTERT表达，显著抑制端粒酶活性、细胞增殖、迁移和侵袭，并在体外诱导宫颈癌细胞凋亡。此外，我们评估了靶向hTERT的siRNA是否影响裸鼠体内肿瘤生长，发现它可显著抑制注射了靶向hTERT的siRNA的小鼠的肿瘤发生和生长。此外，我们还发现敲低hTERT能够显著抑制Akt、PI3K的组成型磷酸化，这可能意味着hTERT的降低在一定程度上通过PI3K/Akt信号通路抑制肿瘤生长。这些结果表明，siRNA抑制hTERT表达可在体外和体内抑制宫颈癌细胞生长，并可能为抗癌基因治疗提供一个新的靶点。
