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Adenovirus-mediated double suicide gene selectively kills gastric cancer cells

Xian-Run Luo1, Jian-Sheng Li, Ying Niu

  • 1Department of Gastroenterology, the First Affiliated Hospital of ZhengZhou University, Zhengzhou, China.

Asian Pacific Journal of Cancer Prevention : APJCP
|May 29, 2012
PubMed

Insights

This study shows that an adenovirus-mediated double suicide gene therapy, using CD/TK and pro-drugs ganciclovir (GCV) and 5-FC, effectively targets and kills gastric cancer cells while sparing normal cells.

Area of Science:

  • Oncology
  • Gene Therapy
  • Molecular Biology

Background:

  • Gastric cancer remains a significant global health challenge.
  • Targeted gene therapy offers a promising approach for selective cancer cell elimination.
  • The survivin promoter shows potential for cancer-specific gene expression.

Purpose of the Study:

  • To evaluate the efficacy of an adenovirus-mediated double suicide gene system (CD/TK) for selective killing of gastric cancer cells.
  • To assess the combined therapeutic effect of the CD/TK system with ganciclovir (GCV) and 5-FC pro-drugs.
  • To investigate the impact on cell cycle progression and tumor growth in vivo.

Main Methods:

  • Adenovirus vectors (Ad-survivin/GFP and Ad-survivin/CD/TK) were used to infect gastric cancer cells (SCG7901) and normal gastric epithelial cells.
  • Gene expression (GFP, CD-TK) was confirmed via fluorescence microscopy and RT-PCR.
  • Cell viability was assessed using MTT assays after pro-drug treatment (GCV and/or 5-FC).
  • Cell cycle analysis was performed using flow cytometry.
  • In vivo efficacy was evaluated in nude mice bearing gastric tumors.

Main Results:

  • Survivin promoter-driven GFP expression and CD/TK gene product were detected specifically in infected SCG7901 gastric cancer cells, not normal cells.
  • Infected gastric cancer cells exhibited high sensitivity to GCV and 5-FC.
  • The CD/TK double suicide gene system demonstrated significantly greater cancer cell killing efficiency (P<0.01) compared to single suicide genes.
  • Treatment led to cell cycle arrest in G0-G1 phase and reduced S phase.
  • Tumor growth in nude mice was significantly inhibited by the double suicide gene system (P<0.01).

Conclusions:

  • Adenovirus-mediated CD/TK double suicide gene therapy, driven by the survivin promoter, is an effective strategy for experimental gastric cancer.
  • This combined therapy with GCV and 5-FC shows superior efficacy compared to single suicide gene approaches.
  • The system offers selective targeting and potent tumor growth inhibition, highlighting its therapeutic potential.

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