Phelps P C, Best C J, Berezesky I K, Merriman R L, Tanzer L R, Boder G B, Trump B F
Department of Pathology, University of Maryland School of Medicine, Baltimore 21201, USA.
Cancer Lett. 1995 Oct 20;97(1):7-15. doi: 10.1016/0304-3835(95)03942-p.
Treatment of NRK-52E (normal) and H/1.2-NRK-52E (Harvey-ras transfected NRK-52E) rat kidney epithelial-like cells with two Eli Lilly antitumor compounds, sulofenur and LY295501 (15.6 microM-1000 microM) resulted in concentration- and time-dependent cell killing. Cytosolic Ca2+ became elevated in both cell lines in the presence of extracellular Ca2+ but only minimally in its absence. Both drugs were more toxic to the tumorigenic cells than to the normal cells, but LY295501 was significantly more toxic to both cells. The similarity in toxic response by both cell lines suggests a similar mechanism of toxic action for both drugs. Since LY295501 is highly toxic to tumorigenic cells but has a manageable dose-limiting toxicity it shows excellent potential for use in chemotherapy.
用礼来公司的两种抗肿瘤化合物舒洛地尔和LY295501（15.6微摩尔至1000微摩尔）处理NRK - 52E（正常）和H/1.2 - NRK - 52E（转染了哈维 - ras基因的NRK - 52E）大鼠肾上皮样细胞，会导致细胞杀伤呈现浓度和时间依赖性。在细胞外钙存在的情况下，两种细胞系的胞质钙均升高，但在其不存在时仅略有升高。两种药物对致瘤细胞的毒性均比对正常细胞大，但LY295501对两种细胞的毒性明显更大。两种细胞系毒性反应的相似性表明两种药物的毒性作用机制相似。由于LY295501对致瘤细胞具有高毒性，但具有可控的剂量限制性毒性，因此它在化疗中显示出极好的应用潜力。
