EFFECT OF METFORMIN AND CISPLATIN COMBINATION THERAPY ON IN VITRO HYPOXIC NEUROBLASTOMA MODEL


Bayrak Ö., Bayrak S., Olgun H. N., Başbınar Y.

10. Onkolojide Arayışlar Sempozyumu, İzmir, Turkey, 16 - 18 December 2022, pp.18-19

  • Publication Type: Conference Paper / Summary Text
  • City: İzmir
  • Country: Turkey
  • Page Numbers: pp.18-19
  • Dokuz Eylül University Affiliated: Yes

Abstract

Introduction and Aim: Neuroblastoma is an extracranial solid tumor of early childhood that has a hypoxic environment. The hypoxic microenvironment causes tumor aggressiveness, cell proliferation, migration effects, radiotherapy, and anti-neoplastic therapy resistance. In many types of cancer, increased levels of insulin cause stimulation of receptors that lead to cell survival and growth signals. For these reasons, metformin is clinically applied as a new potential chemotherapeutic agent. Cisplatin is a potent anti-neoplastic agent containing platinum. These agents specifically inhibit cell proliferation. Cisplatin is frequently used in the clinic alone or combined with other anti-neoplastic agents. This study aimed to examine the effect of cisplatin and metformin combination on cell viability in neuroblastoma cell-line due to the hypoxic microenvironment-induced desensitization of cisplatin, which is used effectively in the clinic in the treatment of neuroblastoma. Materials and Methods: WST-1 reagent was used to determine the IC50 concentration of metformin and cisplatin on the SH-SY5Y cell line. GraphPad 8.0 software was used for IC50 concentration calculation and statistical analysis.

Results: SH-SY5Y cell line was treated with 64-84mM metformin and 1-5uM cisplatin for 48 hours under normoxic and hypoxic conditions. On this cell line, the dose-dependent cytotoxic effects of metformin and cisplatin were 69mM and 3uM, respectively, in normoxic conditions at the 48th hour, and 18mM and 117uM, respectively, in hypoxic conditions. While cisplatin has a cytotoxic effect in the normoxic microenvironment, it has been found to increase cell viability in the hypoxic microenvironment. SH-SY5Y cell line was applied for 48 hours under normoxic and hypoxic conditions. While the cytotoxic effect of cisplatin decreased in hypoxic conditions, its cytotoxic effect increased in combination with metformin. Statistically, a significant difference was observed between cell viability in different microenvironments at the same dose. There is no study in the literature on the combined treatment of metformin and cisplatin under different microenvironmental conditions on the SH-SY5Y cell line. According to the 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 of neuroblastoma.

Keywords: hypoxia, neuroblastoma, metformin, cisplatin