A canalicular multispecific organic anion transporter (cMOAT) antisense cDNA enhances drug sensitivity in human hepatic cancer cells

Koji Koike, Takeshi Kawabe, Toshiya Tanaka, Satoshi Toh, Takeshi Uchiumi, Morimasa Wada, Shin Ichi Akiyama, Mayumi Ono, Michihiko Kuwano

Research output: Contribution to journalArticlepeer-review

247 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5475-5479
Number of pages5
JournalCancer Research
Volume57
Issue number24
Publication statusPublished - Dec 15 1997
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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