College of Medicine, Arizona Cancer Center, University of Arizona, Tucson, AZ 85724-5024, USA.
Anticancer Res. 2011 Sep;31(9):2781-5.
We evaluated mechanisms of interaction between the alkyating agent dacarbazine (DTIC) and the pro-oxidant, imexon, in the human A375 melanoma cell line.
The effect of DTIC and imexon, alone and in combination, was evaluated for growth inhibition (MTT), radiolabeled drug uptake, cellular thiol content (HPLC), and DNA strand breaks (Comet assay). Pharmacokinetic and antitumor effects were evaluated in mice.
Growth inhibition in vitro was additive with the two drugs. There was no effect on drug uptake or on the number of DNA strand breaks. There was a >75% reduction in cellular glutathione and cysteine with imexon but not DTIC. Co-administration of the two drugs in mice caused an increase in the area under the curve of both drugs, but the combination was not effective in reducing human A375 melanoma tumors in vivo.
Imexon and dacarbazine show additive effects in vitro but not in vivo in human A375 melanoma cells.
我们评估了烷化剂达卡巴嗪（DTIC）与促氧化剂依美斯汀在人 A375 黑素瘤细胞系中的相互作用机制。
单独及联合使用 DTIC 和依美斯汀，评估其对细胞生长抑制（MTT）、放射性标记药物摄取、细胞巯基含量（HPLC）和 DNA 链断裂（彗星试验）的影响。在小鼠中评估药代动力学和抗肿瘤作用。
体外生长抑制呈相加作用。药物摄取或 DNA 链断裂的数量没有影响。依美斯汀导致细胞谷胱甘肽和半胱氨酸减少超过 75%，但 DTIC 无此作用。两药联合给药可增加两种药物的曲线下面积，但联合用药在体内对人 A375 黑素瘤肿瘤无疗效。
依美斯汀和达卡巴嗪在体外对人 A375 黑素瘤细胞具有相加作用，但在体内无作用。
