RESUMO
Cancer cells switch from mitochondrial oxidative phosphorylation to glycolysis, even in the presence of normal oxygen concentrations. Inhibition of the glycolytic pathway is therefore a critical strategy in cancer therapy. A non-metabolic glucose analog, 2-deoxy-D-glucose (2-DG), has been the focus of research on glycolytic inhibitors for use in cancer treatment. The current study examined the anti-cancer effects of 2-DG on idarubicin (IDA)-resistant P388 (P388/IDA) leukemia cells. P388/IDA cells were established following continuous exposure of IDA to P388 cells. Characterization of P388/IDA cells revealed increased lactate production and glucose consumption compared with P388 parent cells. The results of a cell viability assay determined that 2-DG induces higher toxicity in P388/IDA cells compared with P388 cells. Although 2-DG also exhibits endoplasmic reticulum (ER) stress-inducing activity, the cytotoxic effect of the ER stress inducer, tunicamycin, on P388/IDA cells was lower than that of P388 cells. A combination of 2-DG and IDA enhanced P388/IDA cell death compared with each agent alone. The results indicated that P388 cells activated glycolysis after acquiring IDA resistance and therefore, inhibition of the glycolytic pathway via 2-DG might be a useful strategy for cancer therapy against IDA- resistant leukemia cells.
RESUMO
PURPOSE: This study aimed to evaluate the effect of chemical exchange saturation transfer (CEST) on the ischemic regions in hypoxic-ischemic encephalopathy (HIE) in comparison with diffusion-weighted imaging (DWI) and magnetic resonance spectroscopy (MRS) using a 7T-MRI. METHODS: We used neonatal rats (n = 8), aged 8 days, to clarify the progression of HIE. The rat model of HIE was developed by ligating and severing the left common carotid artery, followed by 45 minutes of recovery, and 60 minutes of hypoxia (8% O2/92% N2; 34°C). At 0-2 and 24 hours after the onset of HIE, CEST imaging, DWI, and MRS were performed with a 7T-MRI. The magnetization transfer ratio (MTR) asymmetry curves and four MTR asymmetry maps at 0.5, 1.0, 2.0, and 3.5 ppm were calculated using the CEST images. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) maps were calculated by DWI, and brain metabolites were assessed by MRS. RESULTS: In the ischemic regions of neonatal rats, FA was significantly increased at 0-2 hours and decreased at 24 hours after the onset of HIE. ADC in the ipsilateral side was significantly lower than that of contralateral side. All rats with HIE showed hypointense areas on MTR asymmetry maps (2.0 and 3.5 ppm), that did not correspond with the hyperintense areas on DWI. In addition, a significant increase in lactate levels was observed at 0-2 and 24 hours after the onset of HIE. CONCLUSION: CEST MTR maps did not correspond with the hyperintense areas on DWI at 0-2 and 24 hours after the onset of HIE. The change of multi offset CEST signal may be primarily related to the brain metabolites and pH alterations, such as that caused by lactate, after the onset of HIE.