Enhancement of 5-fluorouracil cytotoxicity on human colon cancer cells by retrovirus-mediated interferon-alpha gene transfer.
Gene therapy has advantages in the treatment of a variety of disorders due to its selective expression within specific mammalian cells. Several reports documented the clinical effects of interferon-alpha (IFN-alpha) in management of patients with advanced colorectal carcinoma. We report for the first time, the successful transduction of human IFN-alpha gene into colon cancer cells, COLO 201 using a replication-defective retroviral vector. Retrovirus-containing supernatant from PA 317 packaging cells was used to infect colon cancer cells, COLO 201 and NIH 3T3 cells. Transient infection showed that cell proliferation and cell viability were significantly suppressed in colon cancer cells transduced with IFN-alpha gene. Moreover, IFN-alpha-transduced cells acquired less resistance to 5-FU induced apoptosis. These data demonstrate that IFN-alpha gene transfer may have a clinical application and can be combined with chemotherapy for treatment of advanced colorectal cancer.
Sabaawy
H M
HM
Department of Pharmacology, New York Medical College and Westchester Medical Center, Valhalla, NY 10595, USA.
Ikehara
S
S
Adachi
Y
Y
Quan
S
S
Feldman
E
E
Kancherla
R
R
Abraham
N G
NG
Ahmed
T
T
D016475:3T3 Cells / Q000821:virology; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000502:physiology; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D005472:Fluorouracil / Q000494:pharmacology*; D018014:Gene Transfer Techniques; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D016898:Interferon-alpha; D012333:RNA, Messenger; D005472:Fluorouracil