A canalicular multispecific organic anion transporter (cMOAT) antisense cDNA enhances drug sensitivity in human hepatic cancer cells.
The human cMOAT gene encodes a membrane protein involved in the ATP-dependent transport of hydrophobic compounds. To determine whether cMOAT is associated with drug sensitivity, we transfected an expression vector containing cMOAT antisense cDNA into the HepG2 human hepatic cancer cell line. We observed a reduction in cMOAT protein, as well as an enhanced level of glutathione, in the antisense transfectants. The transfectants displayed an increased sensitivity to cisplatin, vincristine, doxorubicin, and the camptothecin derivatives, (4S)-4,11-diethyl-4-hydroxy-9-[(4-piperidinopiperidino)carbonyl oxy]dione hydrochloride triethydrate and 7-ethyl-10-hydroxycamptothecin, but not to etoposide, 3-[4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosoure a, 5-fluorouracil, and mitomycin C. Results suggest that cMOAT levels are inversely correlated with those of glutathione, and that cMOAT and its related genes may be involved in the sensitivity of cells to certain anticancer agents.
Koike
K
K
Department of Biochemistry, Kyushu University School of Medicine, Maidashi, Fukuoka, Japan.
Kawabe
T
T
Tanaka
T
T
Toh
S
S
Uchiumi
T
T
Wada
M
M
Akiyama
S
S
Ono
M
M
Kuwano
M
M
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D027321:Anion Transport Proteins; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics*; D002945:Cisplatin / Q000494:pharmacology; D016373:DNA, Antisense / Q000235:genetics / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000235:genetics / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D014162:Transfection; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000494:pharmacology
D018528:ATP-Binding Cassette Transporters; D027321:Anion Transport Proteins; D000970:Antineoplastic Agents; D002166:Camptothecin; D002352:Carrier Proteins; D002945:Cisplatin; D016373:DNA, Antisense; D004273:DNA, Neoplasm; D005982:Glutathione Transferase; D000077146:Irinotecan; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D014750:Vincristine