Evaluate The Effect Of 2-deoxy-d-glucose On Multidrug Resistance Reversal By Detecting The Uptake Of ^99mTc-MIBI In Cancer Cells And Its Mechanism

Objective To evaluate the reversal effect of 2-deoxy-D-glucose （2-DG） on multidrug resistance （MDR） by observing the uptake change of ^99mTc-MIBI in cancer cells, and to explore its mechanism.Methods The uptake of ^99mTc-MIBI in HNE^-1/DDP cells under different concentrations of 2-DG were detected by γ-counter, and the clearance rates of ^99mTc-MIBI in HNE^-1 cells, HNE^-1/DDP cells and A549, A549/taxol cells after treated with 2-DG (10 mmol·L^-1) were compared. The content of ATP in HNE^-1/DDP cells after treated with 2-DG. P-glycoprotein （P-gp） and multidrug resistance-associated proteins （MRP） expression were measured by Western blot. Apoptotic HNE^-1/DDP cells treated with Cisplatin（DDP） alone or combined with 2-DG (10 mmol·L^-1) were detected by propidium iodide （PI） staining.Results The clearance rate of ^99mTc-MIBI in HNE^-1/DDP cells after treatment under different concentrations of 2-DG showed a trend of gradually reduce, and when the concentration of 2-DG was 10 mmol·L^-1, the clearance rate reached its minimum level. But when the concentration of 2-DG was 20 mmol·L^-1, the clearance rate did not continue to reduce. The clearance rate of ^99mTc-MIBI in HNE^-1/DDP cells and A549/taxol cells were 54.8% and 49.7%, which was significantly higher than that （-41.3%、-44.9%） in HNE^-1 cells and A549 cells（P<0.01）. The clearance rate of ^99mTc-MIBI in HNE^-1/DDP cells and A549/taxol cells were -203.7% and^-150.3% after treatment 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 apoptotic 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 ^99mTc-MIBI in HNE^-1/DDP and A549/taxol cells. The mechanism may be related with the inhibition of ATP level and reduced expression of P-gp and MRP protein in cancer cells.2-DG combined with chemotherapeutic agents can enhance the apoptosis of cancer cell death.