title: Long-term effects of short hairpin RNA-targeted human telomerase reverse transcriptase on suppression of SGC-7901 cell proliferation by inhibition of telomerase activity.
abstract: Human telomerase reverse transcriptase (hTERT) is an attractive target for cancer gene therapy. However, the poor inhibition of telomerase and a time lag between the inhibition and arrest of cell proliferation limits its use in cancer gene therapy. RNA interference (RNAi) has been proposed as a potential technique for the treatment of cancer with a long-term gene silencing response induced by short hairpin RNA (shRNA). To investigate the long-term effects of telomerase inhibition through the down-regulation of the hTERT gene and the potential role of hTERT in cancer gene therapy, we constructed an shRNA-directed hTERT-expressing vector and introduced it into SGC-7901 cells. A population of cells that stably expressed the shRNA was selected by G418 and continuously cultured in a medium with half the antibiotic concentration for 3 months and the anti-proliferation effects of shRNA-targeted hTERT were then detected. The results showed that shRNA-targeted hTERT significantly inhibited cell proliferation and increased cell apoptosis by down-regulating hTERT expression, thus decreasing telomerase activity. These findings suggest that shRNA-targeted hTERT has long-term anti-proliferation effects on SGC-7901 cells, and it is a potential approach in telomerase-based gene therapy.
authors.affiliation: Department of Pathology, Nanjing Medical University, No. 140 Hanzhong Road, Nanjing City, Jiangsu Province, China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Qian
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
authors.forename: Aiping
authors.initials: A
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Tao
authors.forename: Jianping
authors.initials: J
authors.lastname: Cao
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Feng
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D009690:Nucleic Acid Conformation; D010957:Plasmids / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics*; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics; D014162:Transfection
chemical_list: D034741:RNA, Small Interfering; C509186:TERT protein, human; D019098:Telomerase