Phosphorothioate‑modified antisense oligonucleotides against human telomerase reverse transcriptase sensitize cancer...

Area of Science:

• Oncology
• Molecular Biology
• Gene Therapy

Background:

• Traditional cancer therapies face challenges like resistance, toxicity, and limited efficacy.
• Antisense oligonucleotides targeting human telomerase reverse transcriptase (hTERT) offer a potential strategy to overcome these limitations.
• The combined effect of hTERT-targeting PS-ASODN and irradiation in liver cancer remains largely unexplored.

Purpose of the Study:

• To investigate the synergistic anti-tumor effects of combining hTERT PS-ASODN with irradiation in liver cancer.
• To evaluate the impact of this combination on cell proliferation, viability, senescence, telomerase activity, apoptosis, and DNA damage.

Main Methods:

• Walker 256 liver cancer cells were transfected with hTERT PS-ASODN.
• Cell proliferation and viability assessed using MTT assay.
• Cell senescence evaluated by SA-β-gal staining.
• Telomerase activity measured by TRAP-ELISA.
• Apoptosis analyzed by flow cytometry and DNA damage by comet assay.

Main Results:

• hTERT PS-ASODN inhibited cell proliferation and accelerated senescence by reducing telomerase activity.
• The combination therapy significantly enhanced irradiation-induced inhibition of cell viability and telomerase activity.
• Combined treatment promoted irradiation-induced DNA damage and apoptosis through activation of related proteins.

Conclusions:

• Combined treatment of hTERT PS-ASODN and irradiation demonstrates significant synergistic anti-tumor activity in liver cancer.
• This approach enhances tumor inhibition beyond individual treatments.
• PS-ASODN provides a promising experimental basis for liver cancer gene therapy combined with radiotherapy.