Sodyum dikloroasetat ve sorafenib beraber muamelesinin insan nöroblastomunda sinerjistik etkinliği

Neuroblastoma is the most prevalent malignancy in infants younger than one-year-old. It is an extracranial tumor that nearly accounts for 15 percent of the cancer-related deaths in pediatric cases. Neuroblastoma cells favor glycolysis over oxidative phosphorylation even when oxygen is present to meet high energy demands at a faster rate. Sodium dichloroacetate (DCA) is a pyruvate mimetic able to inhibit pyruvate dehydrogenase kinase enzyme and subsequently glycolysis. Sorafenib (SOR) is a Food and Drug Administration (FDA) approved multikinase inhibitor and is capable of inhibiting angiogenesis. In this study, we focused on evaluating the synergistic efficacy of DCA and SOR co-treatment on human neuroblastoma cells through inhibiting glycolysis and angiogenesis. Firstly synergistic result was demonstrated through cell viability assay and CompuSyn software, which showed up to 70 percent cell proliferation inhibition and a combination index value lower than one respectively. Then Annexin V/PI staining unraveled 69 percent elevation for numbers of late-apoptotic cells upon co-treatment. Immunoblotting analyses showed suppressed glycolysis declined expression of LDH-A levels and inhibited NADH dehydrogenase for cotreated samples compared with the control group. Mitochondrial staining displayed decreases for both mitochondrial mass and inner membrane potential. Lastly, tube formation assay demolished angiogenesis. This study, in conclusion, can be a novel treatment option for deadly neuroblastoma, most importantly by DCA's ability to defeat cell resistance against SOR thereby enhancing the overall efficacy