title: Knockdown of hTERT by siRNA inhibits cervical cancer cell growth in vitro and in vivo.
abstract: 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.
authors.affiliation: Key Laboratory of Pathobiology, Ministry of Education, School of Basic Medical Sciences, Jilin University, Changchun 130021, P.R. China.
authors.forename: Ying-Ai
authors.initials: YA
authors.lastname: Shi
authors.affiliation: Department of Pediatric Surgery, The First Hospital, Jilin University, Changchun 130021, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Pathobiology, Ministry of Education, School of Basic Medical Sciences, Jilin University, Changchun 130021, P.R. China.
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Pathobiology, Ministry of Education, School of Basic Medical Sciences, Jilin University, Changchun 130021, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Du
authors.affiliation: Norman Bethune College of Medical Sciences, Jilin University, Changchun 130021, P.R. China.
authors.forename: Xue-Yao
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Key Laboratory of Pathobiology, Ministry of Education, School of Basic Medical Sciences, Jilin University, Changchun 130021, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: He
authors.affiliation: Key Laboratory of Pathobiology, Ministry of Education, School of Basic Medical Sciences, Jilin University, Changchun 130021, P.R. China.
authors.forename: Shan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Key Laboratory of Pathobiology, Ministry of Education, School of Basic Medical Sciences, Jilin University, Changchun 130021, P.R. China.
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D055785:Gene Knockdown Techniques / Q000379:methods*; D015316:Genetic Therapy; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D009374:Neoplasms, Experimental; D034741:RNA, Small Interfering / Q000378:metabolism*; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000628:therapy*
chemical_list: D034741:RNA, Small Interfering; D019098:Telomerase