Cellular accumulation of the anticancer agent cisplatin: a review.
Acquired resistance to cisplatin (DDP) is a major clinical problem in the treatment of ovarian, testicular, and head and neck carcinomas; decreased accumulation of DDP is the most consistently observed alteration in resistant cells. It has been postulated that DDP enters the cell by passive diffusion based on the observations that DDP accumulation is proportional to the drug concentration, accumulation is not saturable, and that structural analogs of DDP do not inhibit accumulation. However, recent studies show that DDP accumulation can be specifically stimulated or inhibited by pharmacological agents and the activation of signal transduction pathways. This paper reviews the existing data on the mechanism of DDP accumulation and develops the postulate that some component of transport occurs through a gated ion channel.
Gately
D P
DP
Department of Biomedical Sciences, University of California, San Diego, La Jolla 92093-0812.
Howell
S B
SB
D000818:Animals; D002945:Cisplatin / Q000493:pharmacokinetics*; D006801:Humans; D009374:Neoplasms, Experimental / Q000378:metabolism*
D002945:Cisplatin