[Reversal effect and mechanism of lobeline on the multidrug-resistance of human breast cancer cells MCF-7/ADM].
OBJECTIVE
To explore the reversal effect and mechanism of lobeline on the multidrug-resistance (MDR) of human breast cancer cells MCF-7/ADM.


METHODS
In human breast cancer cell line MCF-7/ADM, MTT assay was used to determine the cell growth inhibiting ratio of MCF-7/ADM by ADM and Fu. Fluorospectorphotometer was employed to investigate the intracellular concentration of rhodamine123 to reflect the effect of lobeline on the activity of MDR-related protein P-glycoprotein (P-gp). Taking untreated MCF-7/ADM cells as controls, flow cytometry was applied to detect the intracellular concentration of rhodamine123 in MCF-7/ADM cell intervened with lobeline of 20 micromol/L.


RESULTS
The sensitivity of MCF-7/ADM to ADM and Fu was significantly increased by lobeline in a dose-dependent manner. The inhibitive concentration 50 (IC(50)) of ADM declined from (44.81+/-0.43) mg/L to (16.72+/-0.75) mg/L with a reversion index of 2.68. The IC(50) of Fu declined from (53.12+/-1.60) mg/L to (38.90+/-1.43) mg/L with a reversion index of 1.37. The fluorescence intensity of lobeline-treated cells was significantly higher than that of the controls, when the concentration of lobeline was more than 10 micromol/L. With fewer side effects, the reversal efficacy of 20 micromol/L lobeline was 71.6% of the classical MDR reversal agent of verapamil at the same concentration.


CONCLUSIONS
Lobeline can reverse the MDR of MCF-7/ADM cells by inhibiting the activity of P-glycoprotein.
Chen
Jia
J
Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, China.
Shen
Liangfang
L
Zhou
Rongrong
R
Yao
Wei
W
Zhong
Meizuo
M
Zhu
Zhu Hong
ZH
Zeng
Shan
S
D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006023:Glycoproteins / Q000037:antagonists & inhibitors*; D006801:Humans; D008120:Lobeline / Q000494:pharmacology*
D006023:Glycoproteins; D008120:Lobeline