Caffrey P B, Frenkel G D
Department of Biological Sciences, Rutgers University, Newark, NJ 07102, USA.
Cancer Lett. 1997 Dec 23;121(2):177-80. doi: 10.1016/s0304-3835(97)00349-2.
Previous studies have demonstrated that melphalan-resistant human ovarian tumor cells exhibit a higher degree of sensitivity to the cytotoxic effects of selenite in vitro than comparable drug-sensitive cells (P.B. Caffrey, G.D. Frenkel, Selenite cytotoxicity in drug resistant and non-resistant human ovarian tumor cells, Cancer Res. 52 (1992) 4812-4816; P.B. Caffrey, G.D. Frenkel, The development of drug resistance by tumor cells in vitro is accompanied by the development of sensitivity to selenite, Cancer Lett. 81 (1994) 59-65). We have now examined the sensitivity of drug-resistant tumors to selenite in vivo. A2780 human ovarian tumor cells, or their melphalan-resistant derivative (A2780ME) cells were injected subcutaneously into nude mice and the resulting tumors were found to be melphalan-sensitive and -resistant, respectively, in vivo. Treatment with selenite (2 mg/kg Se s.c.), which had no overt toxic effect on the animals, resulted in a significant decrease in the rate of growth of the melphalan-resistant tumors, but not on the rate of growth of the drug-sensitive tumors. Thus, melphalan-resistant ovarian tumors are also more sensitive to selenite treatment in vivo.
先前的研究表明，与相应的药物敏感细胞相比，耐美法仑的人卵巢肿瘤细胞在体外对亚硒酸盐的细胞毒性作用表现出更高的敏感性（P.B. 卡弗里、G.D. 弗伦克尔，《耐药和非耐药人卵巢肿瘤细胞中的亚硒酸盐细胞毒性》，《癌症研究》52卷（1992年）4812 - 4816页；P.B. 卡弗里、G.D. 弗伦克尔，《肿瘤细胞在体外产生耐药性的同时对亚硒酸盐的敏感性也在增加》，《癌症通讯》81卷（1994年）59 - 65页）。我们现在研究了体内耐药肿瘤对亚硒酸盐的敏感性。将A2780人卵巢肿瘤细胞或其耐美法仑衍生物（A2780ME）细胞皮下注射到裸鼠体内，结果发现所形成的肿瘤在体内分别对美法仑敏感和耐药。用亚硒酸盐（2毫克/千克硒，皮下注射）进行治疗，该剂量对动物没有明显的毒性作用，结果导致耐美法仑肿瘤的生长速率显著降低，但对药物敏感肿瘤的生长速率没有影响。因此，耐美法仑的卵巢肿瘤在体内对亚硒酸盐治疗也更敏感。
