Antitumor effects and radiosensitization of cytosine deaminase and thymidine kinase fusion suicide gene on colorectal carcinoma cells

World J Gastroenterol. 2005 May 28;11(20):3051-5. doi: 10.3748/wjg.v11.i20.3051.

Abstract

Aim: To investigate the killing effect and radiosensitization of double suicide gene mediated by adenovirus on colorectal carcinoma cells.

Methods: Colorectal carcinoma cell line SW480 was transfected with adenovirus expression vector containing cytosine deaminase (CD) and thymidine kinase (TK) fusion gene. The expression of CD-TK fusion gene was detected by reverse transcriptase-polymerase chain reaction. The toxic effect of ganciclovir (GCV) and 5-fluorocytosine (5-FC) on infected cells was determined by MTT assay. The radiosensitization of double suicide gene was evaluated by clonogenic assay.

Results: After prodrugs were used, the survival rate of colorectal carcinoma cells was markedly decreased. When GCV and 5-FC were used in combination, the cytotoxicity and bystander effect were markedly superior to a single prodrug (chi2 = 30.371, P<0.01). Both GCV and 5-FC could sensitize colorectal carcinoma cells to the toxic effect of radiation, and greater radiosensitization was achieved when both prodrug were used in combination.

Conclusion: CD-TK double suicide gene can kill and radiosensitize colorectal carcinoma cells.

MeSH terms

  • Adenoviridae / genetics
  • Artificial Gene Fusion
  • Colorectal Neoplasms / therapy*
  • Cytosine Deaminase / genetics*
  • Genetic Therapy / methods*
  • Humans
  • Prodrugs / therapeutic use*
  • Radiation-Sensitizing Agents / therapeutic use*
  • Thymidine Kinase / genetics*
  • Tumor Cells, Cultured

Substances

  • Prodrugs
  • Radiation-Sensitizing Agents
  • Thymidine Kinase
  • Cytosine Deaminase