Increased sensitivity to cisplatin by nm23-transfected tumor cell lines.
We report a functional link between expression of the metastasis suppressor gene nm23 and cancer cell sensitivity to the alkylating agent cisplatin. Cisplatin was 2-15-fold more inhibitory to the growth in vitro of nm23 transfectants of the K-1735 TK murine melanoma, MDA-MB-435 human breast carcinoma, and OVCAR-3 human ovarian carcinoma cell lines as compared to matched control transfectants. Administration of a single dose of cisplatin i.v. after injection of control- or nm23-1-transfected K-1735 TK melanoma cells resulted in a more pronounced inhibition of pulmonary metastatic colonization by the nm23-1 transfectants. The mechanism of nm23-dependent sensitivity to cisplatin is unknown, but was correlated with increased formation of interstrand DNA cross-links in nm23-H1 transfected breast carcinoma cells. These data suggest that elevation of tumor cell nm23 expression may be considered as a potential therapeutic strategy in combination with cisplatin treatment.
Ferguson
A W
AW
Women's Cancers Section, Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892, USA.
Flatow
U
U
MacDonald
N J
NJ
Larminat
F
F
Bohr
V A
VA
Steeg
P S
PS
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics; D051379:Mice; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D009701:Nucleoside-Diphosphate Kinase; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects
D018906:Antineoplastic Agents, Alkylating; D003432:Cross-Linking Reagents; D004273:DNA, Neoplasm; D054778:NM23 Nucleoside Diphosphate Kinases; D009363:Neoplasm Proteins; D014157:Transcription Factors; C517938:NME1 protein, human; C517939:Nme1 protein, mouse; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins; D002945:Cisplatin