[Transmembrane transport activity of paclitaxel regulated by fangchinoline in MDR1-mDCK II cells].
OBJECTIVE
To research the regulation of transmembrane transport activity of paclitaxel influenced by fangchinoline in MDR1-MDCK II cells.


METHODS
Paclitaxel, one of the substrate of P-gp, was selected as the model drug. Verapamil hydrochloride was adopted as the active control to investigate the bilateral transport activity of paclitaxel regulated by fangchinoline in MDR1-MDCK II cells. RP-HPLC was applied to determine the concentration of paclitaxel in the transporting medium, which was used to calculate apparent permeability coefficient of paclitaxel across MDR1-MDCK I1 monolayer cells.


RESULTS
The efflux rate of paclitaxel was faster than the absorption rates across the MDR1-MDCK II monolayer cells with highly expressed P-gp. The absorption rates of paclitaxel combinated with fangchinoline and verapamil hydrochloride respectively were remarkably increased and the efflux rate was decreased. The reversal effect of the fangchinoline was stronger than the verapamil hydrochloride with the same molar concention.


CONCLUSIONS
Fangchinoline can apparently decrease the efflux of paclitaxel and inhibit the multidrug resistance of antitumor drug mediated by P-gp.
He
Li
L
West China Second Hospital, Sichuan University, Chengdu 610041, China. helisc@163.com
Yang
Junyi
J
Hu
Li'na
L
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D044182:Benzylisoquinolines / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D004285:Dogs; D006801:Humans; D008954:Models, Biological; D017239:Paclitaxel / Q000493:pharmacokinetics*; D010936:Plant Extracts / Q000493:pharmacokinetics*
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D044182:Benzylisoquinolines; D010936:Plant Extracts; C060802:fangchinoline; D017239:Paclitaxel