Combining dichloroacetate with temozolomide increases the antitumor efficacy of temozolomide by inhibiting HIF-1α and promoting p53 signaling pathway

Objective: To investigate the antitumor effect of dichloroacetate (DCA) combined with temozolomide (TMZ) on human glioma in vitro and to explore the mechanism. Methods: In vitro experiments, the inhibitory effects of DCA alone, TMZ alone and DCA/TMZ combination on SHG44 cells were determined by MTT assay. Cell viability was measured by MTT assay; apoptotic cells and intracellular ROS were detected by flow cytometry. The alteration of mitochondrial membrane potential (MMP) was determined by confocal laser scanning microscopy. Western blot was used to detect the expressions of HIF-1α and p53 pathway-related protein in tumor tissues. Results: DCA depolarized mitochondria, increased mitochondrial ROS, and induced apoptosis in human glioma cells in vitro, thus inhibiting cell growth significantly. The inhibition rate of DCA/TMZ combination groups on SHG44 cells growth was significantly higher than that of DCA or TMZ alone. TMZ and DCA decreased the expression levels of HIF-1α and promoted p53 activation in vitro. Conclusion: DCA combined with TMZ inhibits human glioma cells through inhibiting HIF-1α and promoting p53 apoptosis signaling pathway.