Abstract
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)carbonyloxy]dione hydrochloride triethydrate and 7-ethyl-10-hydroxycamptothecin, but not to etoposide, 3-[4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea, 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.
Footnotes
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↵1 This study was supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Education, Science, Sports and Culture of Japan, and by the Fukuoka Anticancer Research Fund.
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↵2 To whom requests for reprints should be addressed. Phone: 81-92-642-6100; Fax: 81-92-642-6203; E-mail: xtckk@biocheml.med.kyushu-u.ac.jp.
- Received August 29, 1997.
- Accepted October 28, 1997.
- ©1997 American Association for Cancer Research.
Volume 57, Issue 24
