title: Synergetic effects of retrovirus IFN-alpha gene transfer and 5-FU on apoptosis of colon cancer cells.
abstract: 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-alpha (IFN-alpha) or the combination of 5-FU plus IFN-alpha on patients with advanced colorectal carcinoma. Therefore, we examined the ability of a retrovirus-mediated IFN-alpha gene transfer to infect colon cancer cells COLO 201 and the effect of IFN-alpha gene expression alone or in combination with other chemotherapeutic drugs as 5-FU. IFN-alpha 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-alpha 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-alpha gene transfer in COLO 201 cells resulted in functional gene expression as assessed by the levels of IFN-alpha mRNA and protein; furthermore, the combination of IFN-alpha 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-alpha gene transfer alone or in combination with other chemotherapeutic drugs for treatment of colorectal cancer.
authors: Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA.
authors: H E
authors: HE
authors: Sabaawy
authors: T
authors: T
authors: Farley
authors: T
authors: T
authors: Ahmed
authors: E
authors: E
authors: Feldman
authors: N G
authors: NG
authors: Abraham
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000628:therapy; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D003110:Colonic Neoplasms / Q000473:pathology* / Q000628:therapy; D018076:DNA, Complementary / Q000235:genetics; D004357:Drug Synergism; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics* / Q000627:therapeutic use; D012190:Retroviridae / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D018076:DNA, Complementary; D016898:Interferon-alpha; D005472:Fluorouracil