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Improved therapeutic effectiveness by combining recombinant p14(ARF) with antisense complementary DNA of EGFR in

Feng Liu1, JinTao Du1, Junming Xian2

  • 1West China School of Medicine, West China Hospital, Sichuan University Department of Otorhinolaryngology, Chengdu, People's Republic of China.

American Journal of Otolaryngology
|November 8, 2015
PubMed
Abstract

Insights

Combining p14(ARF) with antisense EGFR gene therapy significantly inhibited laryngeal squamous cell carcinoma (LSCC) proliferation. This approach offers a potential new gene therapy strategy for LSCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Therapy

Background:

  • Laryngeal squamous cell carcinoma (LSCC) development involves the tumor suppressor p14(ARF) and the proto-oncogene epidermal growth factor receptor (EGFR).
  • Understanding the interplay between p14(ARF) and EGFR is crucial for developing effective LSCC therapies.

Purpose of the Study:

  • To evaluate the therapeutic efficacy of combining recombinant p14(ARF) with antisense complementary DNA of EGFR in LSCC.
  • To determine if this combination therapy enhances antitumor effects compared to individual treatments.

Main Methods:

  • In vitro studies involved infecting Hep-2 cells with recombinant adenoviruses (Ad-p14(ARF) and Ad-antisense EGFR) alone or in combination.
  • Cell proliferation and cell cycle distribution were assessed using MTT assays and flow cytometry.
  • In vivo studies evaluated antitumor effects on Hep-2 xenografts, with protein expression analyzed via western blot.

Main Results:

  • The combination of Ad-p14(ARF) and Ad-antisense EGFR significantly inhibited Hep-2 cell proliferation compared to single treatments (P=0.001, P=0.002).
  • Combined therapy increased the proportion of Hep-2 cells in the G0/G1 phase to 86.9% and led to EGFR down-expression and p14(ARF) over-expression.
  • Significant increases in antitumor activity against Hep-2 xenografts were observed with the combination therapy (P<0.05).

Conclusions:

  • Combination therapy with Ad-p14(ARF) and Ad-antisense EGFR demonstrates significantly enhanced antitumor responses in LSCC.
  • This combined gene therapy approach presents a promising strategy for preventing LSCC proliferation.

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