Ferguson A W, Flatow U, MacDonald N J, Larminat F, Bohr V A, Steeg P S
Women's Cancers Section, Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892, USA.
Cancer Res. 1996 Jul 1;56(13):2931-5.
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.
我们报告了转移抑制基因nm23的表达与癌细胞对烷化剂顺铂敏感性之间的功能联系。与匹配的对照转染细胞相比，顺铂对K-1735 TK小鼠黑色素瘤、MDA-MB-435人乳腺癌和OVCAR-3人卵巢癌细胞系的nm23转染子的体外生长抑制作用要强2至15倍。在注射对照或nm23-1转染的K-1735 TK黑色素瘤细胞后静脉注射单剂量顺铂，结果显示nm23-1转染子对肺转移定植的抑制作用更为明显。nm23依赖的对顺铂敏感性的机制尚不清楚，但与nm23-H1转染的乳腺癌细胞中链间DNA交联形成增加有关。这些数据表明，提高肿瘤细胞nm23的表达可能被视为与顺铂治疗联合使用的一种潜在治疗策略。
