Characterization of glucose uptake dynamics in human U87 glioblastoma cells following co-treatment with palitaxel and dexamethasone
Haley, O'Hara K
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Treatment of cerebral tumors remains a clinical challenge that is complicated by ineffective tumor ablation techniques as well as accompanying side effects, such as peritumoral ederria. Dexamethasone is an effective drug for treating brain edema, but its mechanism and breadth of effects are not fully understood. Paclitaxel has been demonstrated as an effective cytotoxic compound against a number of cancers, including glioblastoma multiforme. However, the effects of co-treatment with a chemotherapeutic and corticosteroid at the cellular level have not been fully explored. This is in part because optical imaging modalities have only recently been developed that provide a spatial resolution high enough to characterize the metabolic dynamics of individual cells. The goal of this study was to determine whether differences in glucose uptake can be used to distinguish metabolically active human glioblastoma cells in culture, for the purpose of comparing the effectiveness of paclitaxel treatment with and without concomitant dexamethasone administration. Fluorescently labeled deoxyglucose (2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose) contrast in vitro is quantified by measuring the rate of mean fluorescence intensity change in cells treated with 2-NBDG using confocal laser-scanning microscopy. Our results show that human U87 glioblastoma cells treated concomitantly with paclitaxel and dexamethasone display a much higher rate of 2-NBDG uptake than when treated with either drug alone. Statistically significant differences were observed across treatment groups, even when changes were measured at the single cell level. The methodologies presented in this study are applicable to myriad disease conditions in which glucose metabolism is altered. We demonstrate that 2-NBDG uptake can serve as a rapid technique for surveying cellular response to chemotherapeutic treatments.
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