[Reversal of multidrug resistance by lomerizine in K562/ADM cells].
OBJECTIVE
To study the effect of lomerizine (Lom) on the reversal of multidrug resistance (MDR) in K562/ADM cells and its mechanism.


METHODS
MTT assay was used to determine the influence of Lom on the cytotoxicity of adriamycin (ADM). The effect of Lom on the apoptosis induced by ADM and vincristine (VCR) in K562/ADM cells was detected using flow cytometry. Intracellular accumulation of ADM was measured by fluorescence spectrophotometry. Flow cytometry was used to investigate the efflux of rhodamine 123 (Rh123) and the expression of P-glycoprotein (P-gp) in K562/ADM cells.


RESULTS
Lom increased the cytotoxicity of ADM and the apoptosis induced by ADM or VCR in K562/ADM cells. At the concentration of 3, 10 and 30 micromol x L(-1), Lom reduced the IC50 value of ADM from 79.03 micromol x L(-1) to 28.14, 8.16 and 3.16 micromol x L(-1), respectively. Lom increased the intracellular accumulation of ADM and inhibited the efflux of Rh123 in K562/ ADM cells. No change in P-gp expression was observed after the treatment of Lom for 72 h.


CONCLUSIONS
Lom had strong reversal effect on MDR in K562/ADM cells by inhibiting P-gp function.
Zhu
Hao-jie
HJ
Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
Wu
Yu-lin
YL
Liu
Guo-qing
GQ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004317:Doxorubicin / Q000378:metabolism* / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D020112:Rhodamine 123 / Q000378:metabolism; D014750:Vincristine / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D002121:Calcium Channel Blockers; D010879:Piperazines; D020112:Rhodamine 123; D014750:Vincristine; D004317:Doxorubicin; C052424:lomerizine