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Discovery of Driver Genes in Colorectal HT29-derived Cancer Stem-Like Tumorspheres
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Discovery of Driver Genes in Colorectal HT29-derived Cancer Stem-Like Tumorspheres

Published on: July 22, 2020

Tumor necrosis factor-related apoptosis-inducing ligand gene on human colorectal cancer cell line HT29

Xiang-Ming Xu1, Chao He, Xiao-Tong Hu

  • 1Department of Colorectal Surgery of the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.

World Journal of Gastroenterology
|April 30, 2003
PubMed
Abstract

Insights

This study demonstrates that a binary adenoviral vector system effectively delivers the Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) gene to colorectal cancer cells. Co-infection with Ad/PGK-GV16 significantly enhanced TRAIL

Area of Science:

  • Oncology
  • Gene Therapy
  • Molecular Biology

Background:

  • Colorectal cancer (CRC) remains a significant global health challenge.
  • Targeted gene therapy offers a promising avenue for CRC treatment.
  • Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) is a potent inducer of apoptosis.

Purpose of the Study:

  • To evaluate the therapeutic efficacy of the TRAIL gene delivered via an adenoviral vector in the human colorectal cancer cell line HT29.
  • To assess the synergistic effect of a binary adenoviral vector system on TRAIL gene delivery and therapeutic outcomes.

Main Methods:

  • Adenoviral vectors (Ad/GT-TRAIL, Ad/GT-Bax, Ad/GT-LacZ, Ad/PGK-GV16) were constructed and amplified.
  • HT29 cells were transfected with Ad/GT-TRAIL, alone or in combination with Ad/PGK-GV16.
  • Bax gene served as a positive control, LacZ as a vector control, and PBS as a mock control.
  • Morphological changes, cell viability (MTT assay), and apoptosis (flow cytometry) were analyzed.

Main Results:

  • Adenoviral vectors achieved a titer of 1X10(10) viral particles/ml.
  • Ad/GT-TRAIL induced significant morphological changes and apoptosis in HT29 cells.
  • Co-infection with Ad/PGK-GV16 markedly enhanced therapeutic efficiency, suppressing HT29 growth by 85.2% and increasing apoptosis to 35.9% (P<0.05).

Conclusions:

  • A binary adenoviral vector system is effective for amplifying and delivering potentially toxic genes like TRAIL.
  • Ad/GT-TRAIL, when co-administered with Ad/PGK-GV16, demonstrates significantly enhanced therapeutic efficiency against HT29 colorectal cancer cells.
  • This binary system effectively induces apoptosis and inhibits the growth of HT29 cells, highlighting its therapeutic potential.

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