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Introduction and Aim: Neuroblastoma is an extracranial solid tumor of early childhood thathas a hypoxic environment. The hypoxic microenvironment causes tumor aggressiveness, cellproliferation, migration effects, radiotherapy, and anti-neoplastic therapy resistance. In manytypes of cancer, increased levels of insulin cause stimulation of receptors that lead to cellsurvival and growth signals. For these reasons, metformin is clinically applied as a newpotential chemotherapeutic agent. Cisplatin is a potent anti-neoplastic agent containingplatinum. These agents specifically inhibit cell proliferation. Cisplatin is frequently used in theclinic alone or combined with other anti-neoplastic agents. This study aimed to examine theeffect of cisplatin and metformin combination on cell viability in neuroblastoma cell-line dueto the hypoxic microenvironment-induced desensitization of cisplatin, which is usedeffectively in the clinic in the treatment of neuroblastoma.Materials and Methods: WST-1 reagent was used to determine the IC50 concentration ofmetformin and cisplatin on the SH-SY5Y cell line. GraphPad 8.0 software was used for IC50concentration calculation and statistical analysis.Results: SH-SY5Y cell line was treated with 64-84mM metformin and 1-5uM cisplatin for 48hours under normoxic and hypoxic conditions. On this cell line, the dose-dependent cytotoxiceffects of metformin and cisplatin were 69mM and 3uM, respectively, in normoxic conditionsat the 48th hour, and 18mM and 117uM, respectively, in hypoxic conditions. While cisplatinhas a cytotoxic effect in the normoxic microenvironment, it has been found to increase cellviability in the hypoxic microenvironment. SH-SY5Y cell line was applied for 48 hours undernormoxic and hypoxic conditions. While the cytotoxic effect of cisplatin decreased in hypoxicconditions, its cytotoxic effect increased in combination with metformin. Statistically, asignificant difference was observed between cell viability in different microenvironments atthe same dose. There is no study in the literature on the combined treatment of metformin andcisplatin under different microenvironmental conditions on the SH-SY5Y cell line. According tothe results, metformin in a hypoxic environment increased the efficacy of cisplatin. It brought forward the idea that it could be used as a new treatment strategy in the treatment ofneuroblastoma.Keywords: hypoxia, neuroblastoma, metformin, cisplatin |
