期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 319, 期 4, 页码 1124-1131出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2004.05.099
关键词
pyronaridine; multidrug resistance; P-glycoprotein; reversal agents; anti-malaria drug; cancer therapy
One of the major mechanisms of multidrug resistance (MDR) in cancer therapy is the overexpression of P-glycoprotein (Pgp). We previously reported that pyronaridine (PND), a synthetic quinoline derivative in the clinic for the treatment of malaria infections, was capable of reversing MDR phenotype in Pgp-overexpressing tumor cells. Here we further evaluated the reversal activity of PND using two Pgp-overexpressing human tumor cell lines: K562/A02 and MCF-7/ADR. PND significantly enhanced the sensitivity of K562/A02 and MCF-7/ADR cells to doxorubicin (DOX), but had no such effect on the parent K562 and MCF-7 cells. The MDR-modulating effect of PND persisted for longer than 24h after removal of the agent from the culture. In nude mice bearing K562/A02 xenografts PND significantly enhanced the antitumor activity of DOX when given intraperitoneally or orally without increasing the toxicity of DOX. Our observations suggest that PND represents a promising agent for overcoming MDR in cancer therapy. (C) 2004 Elsevier Inc. All rights reserved.
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