科研之友
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摘要
Context: Earlier studies have shown that cytotoxicity of glycolic inhibitor 2-deoxy-D-glucose is heterogeneous among different tumor cell lines due to a number of reasons including difference in p53 status. %26lt;br%26gt;Aim: To investigate the cytotoxic effects of 2-DG in isogenic cell systems that differ in their p53 status. %26lt;br%26gt;Material and Methods: Head and neck carcinoma cells KB and its two p53 mutants (KB68-mutation in transactivation domain (Arg/Cys) at position 68 and KB110-mutation in proline rich deoxyribonucleic acid binding domain (Glu/Gly) at position 110) were used as the model. Clonogenecity, cell proliferation, cell cycle, annexin V assay, intracellular levels of ROS and NADP+/NADPH levels were investigated as parameters for 2-DG induced cytotoxicity. %26lt;br%26gt;Results: Macrocolony assay showed that the cytotoxicity of 2-DG was time-and concentration-dependent. However, the sensitivity of the three cell lines were quantitatively different, with KB110 being more sensitive than the parental cell line KB and KB68. The effects of 2-DG on growth inhibition, cell cycle, and apoptosis correlated well with the changes in cell survival in these cells. A higher degree of 2-DG induced enhancement in the metabolic oxidative stress was evident in both the mutant cell lines (elevated ROS level and NADP+/NADPH ratio) suggestive of a higher degree of compromize in the antioxidant defense in the mutant cells. %26lt;br%26gt;Conclusions: 2-DG could be considered as a potential therapeutic agent that induces cell death (which could be linked to induced oxidative stress) selectively in tumors with p53 mutations (particularly in the proline rich region).
- 出版日期2013-12
