title: Telomerase inhibition strategies by siRNAs against either hTR or hTERT in oral squamous cell carcinoma.
abstract: Human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT) are considered effective molecular targets for current anticancer therapy. In this study, we investigated the therapeutic effects of targeting hTR and hTERT individually or in combination by recombinant adenovirus-delivered small interfering RNA (siRNA) in oral squamous cell carcinoma (OSCC) Tca8113. Further, we screened the optimal strategy for RNA interference. Our results show that these different recombinant adenoviruses specifically reduced the levels of hTR mRNA, hTERT mRNA, hTERT protein and telomerase activity in Tca8113 cells. Moreover, they successfully inhibited xenograft tumor growth in nude mice. The potency of their antitumor activities was ranked as follows: anti-hTR >anti-hTR+anti-hTERT >anti-hTERT. Therefore, we demonstrated that the siRNA-expressing recombinant adenoviruses were an effective anticancer tool for treatment of OSCC. Furthermore, the anticancer effect of solely targeting hTR was more direct and efficient, compared with the effect of targeting hTR and hTERT in combination, or hTERT exclusively. The mechanism of this anticancer effect in OSCC was not only related to the inhibition of cell proliferation and the induction of cell apoptosis, but might also involve the inhibition of tumor angiogenesis.
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.forename: G
authors.initials: G
authors.lastname: Yao
authors.forename: N
authors.initials: N
authors.lastname: Geng
authors.forename: Y
authors.initials: Y
authors.lastname: Xie
authors.forename: Y
authors.initials: Y
authors.lastname: Feng
authors.forename: P
authors.initials: P
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Kong
authors.forename: J
authors.initials: J
authors.lastname: Xue
authors.forename: S
authors.initials: S
authors.lastname: Cheng
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: L
authors.initials: L
authors.lastname: Xiao
mesh_terms: D000256:Adenoviridae; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000628:therapy*; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000235:genetics / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000235:genetics; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000627:therapeutic use*; D019098:Telomerase / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D017931:DNA Primers; D034741:RNA, Small Interfering; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase