Increased Sensitivity to Cisplatin by nw23-transfected Tumor Cell Lines

We report a functional link between expression of the metastasis sup pressor gene nnil.l and cancer cell sensitivity to the alkylating agent cisplatin. Cisplatin was 2-15-fold more inhibitory to the growth in vitro of IIIII2.Ìtransfectants of the K-1735 IK 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 controlor nm2J-/-transfected K-1735 TK melanoma cells resulted in a more pronounced inhibition of pulmonary metastatic colonization by the nm23-l transfectants. The mechanism of n/n2J-dependent sensitivity to cisplatin is unknown, but was correlated with increased formation of interstrand DNA cross-links in IIHI2.Ì-IIItransfected 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.