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Double suicide genes driven by kinase domain insert containing receptor promoter selectively kill human lung cancer

Junrong Ma1, Mi Li1, Longyong Mei2

  • 1Laboratory of Endocrinology and Metabolism, West China Hospital, Sichuan University, P.R. China, 610041.

Genetic Vaccines and Therapy
|March 23, 2011
PubMed
Abstract

Insights

This study shows that a double suicide gene system, driven by the KDR promoter, effectively targets and kills KDR-expressing tumor cells. This gene therapy approach significantly reduces tumor growth in preclinical models.

Area of Science:

  • Molecular Biology
  • Cancer Gene Therapy
  • Oncology

Background:

  • Investigating novel gene therapy strategies for cancer.
  • Evaluating the efficacy of double suicide gene systems.
  • Targeting tumors with specific molecular markers.

Purpose of the Study:

  • To assess the selective killing efficacy of a double suicide gene system.
  • To utilize the KDR promoter for targeted gene delivery.
  • To evaluate the system's effectiveness in lung and liver cancer models.

Main Methods:

  • Constructed a double suicide gene system (pcDNA3-KDRp-CDglyTK).
  • Transfected lung (L9981, NL9980) and liver (HepG2) cancer cell lines.
  • Assayed in vitro proliferation/apoptosis and in vivo xenograft tumor growth.

Main Results:

  • Gene expression (CD and TK) was specific to KDR-positive cells (L9981, NL9980).
  • Treatment with 5-Fc and GCV reduced proliferation and increased apoptosis in targeted cells.
  • Significant tumor growth inhibition was observed in vivo.

Conclusions:

  • KDR promoter-driven CDglyTK gene expression offers a targeted gene therapy strategy.
  • This approach demonstrates effective selective killing of KDR-expressing tumors.
  • Potential for treating tumors with intrinsic KDR expression.

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