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[Cancer Research 57, 5475-5479, December 15, 1997]
© 1997 American Association for Cancer Research
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A Canalicular Multispecific Organic Anion Transporter (cMOAT) Antisense cDNA Enhances Drug Sensitivity in Human Hepatic Cancer Cells1

Koji Koike2, Takeshi Kawabe, Toshiya Tanaka, Satoshi Toh, Takeshi Uchiumi, Morimasa Wada, Shin-ichi Akiyama, Mayumi Ono and Michihiko Kuwano

Department of Biochemistry, Kyushu University School of Medicine, 3-1-1 Maidashi, Fukuoka 812-82 [K. K., T. K., T. T., S. T., T. U., M. W., M. O., M. K.], and Department of Cancer Chemotherapy, Institute for Cancer Research, Faculty of Medicine Kagoshima University, Sakuraga-oka 890 [S. A.], Japan

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.

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.

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 8/29/97. Accepted 10/28/97.




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