Gene transfer has advantages in the treatment of a variety of disorders due to its selective expression within specific mammalian cells including the most primitive stem cells and cancer cells. Several investigators have reported on the clinical effects of interferon-α (IFN-α) or the combination of 5-FU plus IFN-α on patients with advanced colorectal carcinoma. Therefore, we examined the ability of a retrovirus-mediated IFN-α gene transfer to infect colon cancer cells COLO 201 and the effect of IFN-α gene expression alone or in combination with other chemotherapeutic drugs as 5-FU. IFN-α showed positive antitumor activity against COLO 201 cells, whereas 5-FU showed time- and concentration-dependent antitumor activity against COLO 201 cells. Furthermore, we demonstrated that combination therapy of IFN-α gene transfer and 5-FU resulted in enhancement of cancer cell lethality. The potentiation increased with higher concentrations of 5-FU by 1.5- to 2.1-fold. Our results suggest that retrovirus-mediated IFN-α gene transfer in COLO 201 cells resulted in functional gene expression as assessed by the levels of IFN-α mRNA and protein; furthermore, the combination of IFN-α gene transfer and 5-FU have additional effects on the induction of apoptosis. This finding provides an experimental basis for possible clinical therapy using retrovirus-mediated IFN-α gene transfer alone or in combination with other chemotherapeutic drugs for treatment of colorectal cancer.

Keywords:
Colon cancer, 5-Fluorouracil, Gene transfer, Interferon-α
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