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.