Reversal effect of delavirdine on multidrug resistance-associated protein 2-mediated multidrug resistance
10.3760/cma.j.issn.1008-6315.2009.06.020
- VernacularTitle:地拉夫定对多药耐药相关蛋白2介导的多药耐药逆转作用研究
- Author:
Meng LI
;
Xiaodong MEI
- Publication Type:Journal Article
- Keywords:
Delavirdine;
cMOAT;
Multidmg resistance;
Apoptosis
- From:
Clinical Medicine of China
2009;25(6):618-622
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the effect and the possible mechanism of delavirdine on muhidrng resist-ance-aasociated protein 2(MRAP2)-mediated multidrug resistance in LLC/cMOAT cells. Methods MTT assay was used to determine the effects of delavirdine on proliferation of LLC/CMV and LLC/cMOAT cells. The inhibitory effects of vincristine (VCR),cisplatin (DDP),adriamycin (ADM) and etoposide (VP-16) used alone or in combi-nation with delavirdine on the proliferation of LLC/CMV and LLC/cMOAT cells were evaluated by MTT assay. The cell cycle distribution, the apoptosis rate of the cells treated with different concentration of delavirdine and the intra-cellular concentration of ADM were determined by flow cytometry (FCM). Results Delavirdine at the concentration of 4 μmol/L and below showed no significant cytotoxicity to LLC/CMV and LLC/cMOAT cells. The resistance of LLC/cMOAT cells to VCB, VP-16, ADM and DDP were 9.58,1.11,2.98 and 3.96 folds of that of LLC/CMV cells. When 2 μmol/L delavirdine was added, the resistance was 5.21 and 2.55 folds respectively;when 4 μmol/L dela-virdine was edded,the resistance was 7.56 and 3.03 ,while 2,4 μmol/L delavirdine made no significant changes to the chemosensitivity of LLC/CMV cells to VCR and DDP(P>0.05). Cellular cycle analysis demonstrated that 0,6, 12,24 hours after co-cultured with delavirdine the amount of cells at G1 phase increased from(38.92±0.15)% to (56.87±2.23)%,(65.36±2.76)% and (74.77±5.06)%. The cell apoptosis rate increased from 1.77% to 17.45% and 28.52% when treated with delavirdine at 2,4 μmol/L and VCR for 24 h. When treated with 2,4 μmol/L delavirdine, ADM accumulation in LLC/cMOAT cells was enhanced significantly(P<0.05). Conclusion DLV can partially reverse the multidrng resistance of LLC/cMOAT cells, and the reverse effect correlates to the concentration. The possible mechanism may involve the growth arrest at G1, increasing of intracellular drug concen-tration and promoting apoptosis.
