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[Inhibition of hTR activity for suppression of lung cancer cell proliferation using antisense phosphorothioate
1Centre of molecular Biology, Tianjin Medical University, Tianjin 300070, China.
Objective:
Telomerase activity was measured in 8 lung tumor cell lines and transfected antisense phosphorothiate oligodeoxynucleotides (anti-PS-ODN) of hTR as therapeutic agents into target cell LTEP-a-2 to investigate the inhibitory effect on telomerase activity and tumor cell growth.
Methods:
1. Telomerase activity assay in 8 human lung tumor cell lines using telomerase PCR ELISA. 2. Synthesized anti-PS-ODNs of hTR and random PS-ODN transfected with Clonfectin into LTEP-a-2 cell lines for 72 hr. 3. Measure telomerase activity by telomerase PCR ELISA, SDH activity by MTT assay and cell growth.
Results:
Eight cell lines showed positive expression of telomerase activity. Various anti-PS-ODNs could inhibit telomerase activity, SDH activity and cell growth. The inhibition became more marked with the increase of anti-PS-ODNs concentrations. Concentrations of 5 - 40 micromol/L anti-PS-ODNs of hTR specifically reduced the telomerase activity by 25.7% - 84.0%. PS-ODNs of anti-hTR were also able to reduce SDH activity by 19.4% - 74.7% at 5 - 40 micromol/L. The dose of 5 - 40 micromol/L PS-ODNs of anti-hTR had the ability to inhibit cell growth by 14.8% - 72.5%. The results indicate that random sequence of PS-ODN(9) failed to inhibit telomerase, SDH activity and cell growth. A statistically significant difference exists between random PS-ODN and three anti-PS-ODNs (P < 0.01).
Conclusions:
Human lung tumor cell lines express high telomerase activity. PS-ODNs of anti-hTR had the ability to inhibit telomerase and reduce LTEP-a-2 cell growth and metabolism.
Insights
Antisense phosphorothioate oligodeoxynucleotides targeting human telomerase RNA (anti-hTR) effectively inhibited telomerase activity and lung tumor cell growth. These findings suggest anti-hTR as a potential therapeutic agent for lung cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Context:
- Telomerase is a key enzyme in cancer, promoting cell immortality.
- Lung tumor cell lines exhibit high telomerase activity.
- Targeting telomerase offers a potential therapeutic strategy for lung cancer.
Purpose:
- To evaluate the efficacy of antisense phosphorothioate oligodeoxynucleotides (anti-PS-ODN) targeting human telomerase RNA (hTR) as a therapeutic agent.
- To investigate the inhibitory effects of anti-hTR on telomerase activity and lung tumor cell growth in vitro.
Summary:
- Telomerase activity was assessed in eight human lung tumor cell lines.
- Synthesized anti-hTR and random PS-ODN were transfected into LTEP-a-2 cells.
- Telomerase activity, succinate dehydrogenase (SDH) activity, and cell growth were measured.
- Anti-hTR significantly inhibited telomerase activity (25.7%-84.0%), SDH activity (19.4%-74.7%), and cell growth (14.8%-72.5%) in a dose-dependent manner.
- Random PS-ODN showed no significant inhibitory effects.
Impact:
- Demonstrates the potent inhibitory effect of anti-hTR on lung tumor cell proliferation and metabolism.
- Highlights the potential of anti-hTR as a targeted therapy for lung cancer.
- Provides evidence for the specific targeting of telomerase in cancer treatment.