Cimetidine enhances the antiproliferative effect of 5-fluorouracil on colon carcinoma SW620.
We investigated the effects of cimetidine on p-glycoprotein and on the antiproliferative effect of various anticancer drugs which are recognized by p-glycoprotein. We used colon carcinoma SW620 cells and their doxorubicin resistant SW620 Ad300 derived cells, the latter express p-glycoprotein and have multidrug resistance phenotype. To assess the effect of cimetidine on the efflux activity of p-glycoprotein, we examined its effects on the accumulation of rhodamine123 which is recognized by p-glycoprotein. Cimetidine had no effect on rhodamine123 accumulation on either cell line. Cimetidine did not enhance the antiproliferative effect of any of the anticancer drugs investigated. This indicates that cimetidine was not recognized by p-glycoprotein. However, cimetidine remarkably enhanced the antiproliferation effects of 5-fluorouracil on SW620 cells, not those of 5-fluorouracil on SW620 Ad300, whereas cimetidine itself showed little effect on antiproliferation. This finding indicates that combination therapy using 5-fluorouracil and cimetidine might be useful for cancer patients.
Komatsubara
M
M
SmithKline Beecham Seiyaku K.K., Tokyo, Japan.
Nagata
T
T
Miyauchi
S
S
Kamo
N
N
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002927:Cimetidine / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D020112:Rhodamine 123 / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000964:Antimetabolites, Antineoplastic; D020112:Rhodamine 123; D002927:Cimetidine; D005472:Fluorouracil