Targeted therapy of human laryngeal squamous cell carcinoma in vitro by antisense oligonucleotides directed against

Zezhang Tao1, Shiming Chen, Zhanyuan Wu

  • 1Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China. shimingchen0468@hotmail.com

Insights

Antisense oligonucleotides targeting human telomerase reverse transcriptase (hTERT) mRNA effectively reduced telomerase activity and promoted cancer cell death. This approach shows promise for treating laryngeal squamous carcinoma.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Telomerase is a key enzyme in cancer cell proliferation.
  • Inhibiting telomerase activity is a potential cancer treatment strategy.
  • Human telomerase reverse transcriptase (hTERT) mRNA is a target for telomerase inhibition.

Purpose of the Study:

  • To investigate the effect of antisense oligonucleotides (ODNs) targeting hTERT mRNA in a laryngeal cancer cell line (Hep-2).
  • To evaluate the potential of anti-hTERT ODNs as a therapeutic modality for laryngeal squamous carcinoma.

Main Methods:

  • Synthesis of a 20mer antisense oligodeoxynucleotide (anti-hTERT) and a mismatched control.
  • Treatment of Hep-2 cells with ODNs for up to 72 hours.
  • Assays used: RT-PCR for hTERT mRNA, TRAP for telomerase activity, MTT for cell viability, H&E staining for morphology, and flow cytometry for cell cycle analysis.

Main Results:

  • Antisense treatment significantly decreased hTERT mRNA expression and telomerase activity.
  • Cell growth rate and viability were reduced following antisense treatment.
  • Increased apoptosis and morphological changes indicative of cell death were observed.

Conclusions:

  • Short-term antisense treatment targeting hTERT mRNA effectively inhibits telomerase activity in Hep-2 cells.
  • This inhibition leads to apoptotic cell death.
  • Anti-hTERT ODNs represent a potential treatment strategy for laryngeal squamous carcinoma.

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