Effect of antisense oligodeoxynucleotide of telomerase RNA on telomerase activity and cell apoptosis in human colon cancer

Human telomerase is absent in most normal tissues, but is abnormally activated in all major cancer cells. Telomerase enables tumor cells to maintain telomere length, allowing indefinite replicative capacity. Albeit not sufficient in itself to induce neoplasia, telomerase is believed to be necessary for cancer cells to grow without limit. Studies using an antisense oligonucleotide (ASODN) to the RNA component of telomerase or human telomerase reverse transcriptase (hTERT) demonstrate that telomerase in human tumor lines can be blocked in vivo. Inhibition of hTERT led to telomere shortening and cancer cell death, validating telomerase as a target for anticancer genetic therapy. Varieties of approaches for hTERT inhibition have been investigated. The aim of this study was to analyze the biological activity of ASODN to the hTERT mediated by retrovirus vector, which was used as therapy for ovarian tumor. We constructed and characterized a recombinant retrovirus vector with full-length hTERT antisense complementary DNA. The vector was introduced into ES-2 by lipofectamine-mediated gene transfection. The cellular proliferation and telomerase activity of the transformant cells were retarded. The hTERT gene expression and the telomerase activity of the transformant cells were both decreased. The transformant cells show partial reversion of the malignant phenotype. PT67 cells were also transfected with the recombinant vector and virus-producer cells were generated. The retrovirus-containing supernatant effectively inhibited the growth of human ovarian tumor xenografts in mouse models (subcutaneous tumor model), and enhanced the mouse survival time.

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In vitro and in vivo tumor suppressive activity induced by human telomerase transcriptase-targeting antisense oligonucleotides mediated by cationic liposomes

Han

Chen

et al. 2008

Journal of Bioscience and Bioengineering

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Effect of antisense oligodeoxynucleotide of telomerase RNA on telomerase activity and cell apoptosis in human colon cancer

Abstract: As-ODN can specifically inhibit the telomerase activity of SW480 cells and induce apoptosis.

Cited by 5 publications

References 26 publications

Synergistic down-regulation of telomerase by all-trans retinoic acid and antisense oligonucleotide in oral squamous cell carcinoma cell line (Tca8113)

Synergistic down-regulation of telomerase by all-trans retinoic acid and antisense oligonucleotide in oral squamous cell carcinoma cell line (Tca8113)

Inhibition of human telomerase reverse transcriptase in vivo and in vitro for retroviral vector-based antisense oligonucleotide therapy in ovarian cancer

In vitro and in vivo tumor suppressive activity induced by human telomerase transcriptase-targeting antisense oligonucleotides mediated by cationic liposomes

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