Reversal of P—glycoprotein—mediated multidrug resistance by pyronaridine

An association between P-glycoprotein(Pgp) level and poor clinical outcome has been found.Efforts have been made to search for the modulators of tumor multidrug resistance (MDR) from the components of Chinese herbs and the molecules developed in China.Pyronaridine (PND)was found to be able to reverse MDR to doxorubicine(DOX) in K562/A02 and MCF7/ADR,expressing Pgp with more efficacy than verapamil.PDN increased the accumulation of DOX and reduced efflux of Rh123 in the two cell lines.The reversibility prersisted for at least 24h after removel of the drug from the culture medium.When administered orally or parenterally,PND significantly enhanced the in vivo antitumor activity of DOX in K562/A02 xenografts,but did not significantly increase the toxicity or alter the plasma pharmacokinetics of DOX.In view of PND has been safely used in clinic for the treatment of malaria for more than 20 years at high dose,the modulator might be the promision in the reversal of MDR in the clinic.