nica中琦麓学报.PDFVIP

BK~ ID，ISSN0259—9756 AczaPharmmcolo~dcaSinica 中■琦麓学报 Restoration ofintracellular drugaccum ulation in M DR celllineK562r doesnotmean reversalofitsdrugresistna ce HU xus。cHEN W an—Yuan (CancerInstitute，ZhefiangMedicalUniversity，Hangzhou310009，China) ABSTRACT 0ur purpose was to test P—glyocproteinincancercells，whichmediated whether drug sensitivity and dur g accum ula— theenergy-dependentdrug effluxofintracel- tioninM DR cellerythroleukemicK562rcould lulardrugs，wasgenerally cons ideredassma- berestoredbyincubatingceilswith3anthra— jormechanism ofdrugresistance[2]． Though cyclineantibioticsincombination． Drugsen— mostofthetypicalM DR cancercelllineses— sl。tl。vltl。esofcellswereassessedwithM TT as— tablishedinvitroexhibitedadecreaseofintra— say， in which doxorubicint epirubicin， cellular drug accumulation andan incresseof daunorubicin，orthe3-drug mixturewasap— intracellulardurgretention，themagnitudeof plied with concentrationsranging from 1 to reduceddruguptakewasobviouslynotenough 3125ng ·ml～． TheIC5oofK562rcellswere toaccountforthedrugresistanceacquiredby 1．0，1．0，0．1，and 0．2big ·ml～ ，respective— thedurg—resistantcells啪． Theratiosofdox— lytabout 22， 16，10，and 20 times higher ourbicin between nucleus and cytoplasm in thanthoseofK562cells． Aftercellswereex— drug—resistantcellswere1／2to1／3foIdsless posed to doxorubicin (2— 32Pg ·rM )for 1 than those in their parent drug-sensitive h，thedrugconcentrationsinK562rcellswere cellsc ． The ratiosofDNA—bound doxoru— sllhigherthan thosein K562cells． Simitar bicintofreedoxorubicin indrug—-resistantcan—． results were obtained for epiurbicin or cercellswereone orderlower than those in daunorubicin． After 1-h incubation ofcells theirdrug—sensitivecells ． The drug sensi- withthe3-drugmi