A molecular basis for multidrug-resistance and reversal of resistance with human malignant cells

S. Akiyama, H. Kikuchi, A. Yoshimura, M. Matsumoto

研究成果: Review article査読

抄録

Development of cellular resistance to multiple types of anticancer agents has been recognized as one of the major obstacles for the effective cancer chemotherapy. Increased expression of mdr 1 mRNA seems to be a common mechanism for multidrug resistance (MDR) in human malignant cells. The product of the mdr 1 gene is P-glycoprotein. The predicted membrane orientation of the protein and homology with bacterial active transport proteins, and capability of the protein to bind hydrophobic anticancer agents are consistent with the function of P-glycoprotein as an energy-dependent efflux pump responsible for MDR phenotype. Most of the hydrophobic agents which overcome MDR are cationic and amphipathic. These agents interact with certain polar lipids and inhibit also the binding of hydrophobic anticancer agents with P-glycoprotein. They might directly bind to the binding site of anticancer agents on P-glycoprotein and competitively inhibit the binding of anticancer agents. Alternatively, they might bind to polar lipids of membrane vesicles and indirectly inhibit the binding ability of the protein to anticancer agents by perturbing the membrane function.

本文言語English
ページ(範囲)2617-2625
ページ数9
ジャーナルJapanese Journal of Cancer and Chemotherapy
14
9
出版ステータスPublished - 1987 9 1
外部発表はい

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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