Double suicide genes selectively kill human umbilical vein endothelial cells

Area of Science:

• Molecular Biology
• Gene Therapy
• Oncology

Background:

• Developing novel gene therapy strategies is crucial for cancer treatment.
• Targeting tumor angiogenesis is a key therapeutic approach.

Purpose of the Study:

• To construct a recombinant adenovirus carrying CDglyTK double suicide genes under the KDR promoter.
• To evaluate the efficacy of this system in targeting KDR-expressing cells and suppressing tumor angiogenesis.

Main Methods:

• Constructed recombinant adenoviruses (AdKDR-CDglyTK) using KDR promoter and CDglyTK genes.
• Infected KDR-positive (ECV304) and KDR-negative (HepG2) cells with AdKDR-CDglyTK at varying multiplicities of infection (MOI).
• Assessed cell viability and killing effects using annexin V-FITC and TUNEL staining after prodrug (GCV and/or 5-FC) treatment.

Main Results:

• Successfully constructed and efficiently delivered AdKDR-CDglyTK via recombinant adenoviruses.
• Demonstrated high sensitivity of KDR-expressing ECV304 cells to GCV and 5-FC, with cell death dependent on MOI and prodrug concentration.
• Observed no significant killing effect on KDR-negative HepG2 cells, highlighting the system's specificity.
• Found that combining GCV and 5-FC was more effective than single prodrugs, and suppressed transgenic ECV304 cell growth.

Conclusions:

• The AdKDR-CDglyTK system combined with double prodrugs is a potentially effective strategy for suppressing tumor angiogenesis.
• This gene therapy approach shows promise for targeted cancer treatment by selectively eliminating endothelial cells within tumors.