Evaluation of reversal effect of 2-DG on multidrug resistance by detecting uptake of 99mTc-MIBI in HNE-1/DDP cells
10.3969/j.issn.1001-1978.2015.10.021
- VernacularTitle:99mTc-MIBI评价2-脱氧-D-葡萄糖对鼻咽癌耐药株多药耐药的逆转作用及机制
- Author:
Yong SHEN
;
Weili SUN
;
Chao YUAN
;
Huiqin XU
;
Bin LIU
- Publication Type:Journal Article
- Keywords:
multidrug resistance;
99m Tc-MIBI;
2-de-oxy-D-glucose;
nasopharyngeal carcinoma;
reversal;
P-gp;
MRP
- From:
Chinese Pharmacological Bulletin
2015;(10):1433-1438
- CountryChina
- Language:Chinese
-
Abstract:
Aim To evaluate the reversal effect of 2-deoxy-D-glucose ( 2-DG ) on multidrug resistance ( MDR) by observing the uptake change of 99m Tc-MIBI in HNE-1/DDP cells, and to explore its mechanism. Methods The uptake of 99m Tc-MIBI in HNE-1/DDP cells under different concentrations of 2-DG was detec-ted by γ-counter, and the clearance rates of 99m Tc-MI-BI in HNE-1 cells and HNE-1/DDP cells after treated with 2-DG (10 mmol·L-1 ) were compared. The con-tent of ATP in HNE-1/DDP cells was detected after treated with 2-DG. P-glycoprotein ( P-gp ) and multi-drug resistance-associated proteins ( MRP ) expression were measured by Western blot. Apoptotic HNE-1/DDP cells treated with DDP alone or combined with 2-DG (10 mmol·L-1 ) were detected by propidium io-dide ( PI ) staining. Results The clearance rate of 99m Tc-MIBI in HNE-1/DDP cells was 54. 8%, which was significantly higher than that ( - 41. 3%) in HNE-1 cells (P<0. 01). The clearance rate of 99mTc-MIBI in HNE-1/DDP cells was -203. 7% after treat-ment with 2-DG ( 10 mmol · L-1 ) , which could be significantly reduced compared with the control group ( P<0. 01 ) . The level of ATP was 55 . 69% compared with the negative control group and the expression of P-gp and MRP protein decreased dramatically in HNE-1/DDP. With the combination of 2-DG and DDP, the ap-optotic rate of HNE-1/DDP cells reached 49 . 4%which was significantly higher than DDP treated group (22. 5%) . Conclusion Multidrug resistance and the reversal effect of 2-DG on multidrug resistance could be evaluated effectively by detecting the uptake change of 99m Tc-MIBI in HNE-1/DDP cells. The mechanism may be related with the inhibition of ATP level and the re-duced expression of P-gp and MRP protein in cancer cells.
