Reversal effect and mechanism of lobeline on the multidrug-resistance of human breast cancer cells MCF-7/ADM.
- Author:
Jia CHEN
1
;
Liangfang SHEN
;
Rongrong ZHOU
;
Wei YAO
;
Meizuo ZHONG
;
Zhu Hong ZHU
;
Shan ZENG
Author Information
1. Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, China.
- Publication Type:Journal Article
- MeSH:
Breast Neoplasms;
pathology;
Cell Line, Tumor;
Drug Resistance, Multiple;
drug effects;
Drug Resistance, Neoplasm;
drug effects;
Female;
Glycoproteins;
antagonists & inhibitors;
Humans;
Lobeline;
pharmacology
- From:
Journal of Central South University(Medical Sciences)
2009;34(8):738-743
- CountryChina
- Language:Chinese
-
Abstract:
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.
CONCLUSION:Lobeline can reverse the MDR of MCF-7/ADM cells by inhibiting the activity of P-glycoprotein.
