Modulation of p53 expression by human recombinant interferon-alpha2a correlates with abrogation of cisplatin resistance in a human melanoma cell line.
G3361/CP cells, a cisplatin (CDDP)-resistant subclone of the human melanoma cell line G3361, overexpress wild-type p53 protein and demonstrate an increase in the percentage of cells in G0--G1 arrest compared to parental cells. Exposing G3361/CP cells to human recombinant IFN-alpha2a reduces the high basal levels of p53, releases G3361/CP cells from G0-G1 into S phase, and abrogates CDDP resistance. These findings suggest that recombinant IFN-alpha2a disrupts p53-mediated cell cycle regulation to restore CDDP sensitivity in G3361/CP cells.
Davol
P A
PA
Department of Medicine, Roger Williams Medical Center, Providence, Rhode Island 02908, USA.
Goulette
F A
FA
Frackelton
A R
AR
Darnowski
J W
JW
D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage*; D004249:DNA Damage; D004351:Drug Resistance; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016158:Genes, p53; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D008545:Melanoma / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin