Optimization of epi-drug combination against glioblastoma multiform cell line (u251) using response surface methodology

Morvarid Soleiman,1 Mehrnoosh fathi-roudsari,2,* Amir maghsoudi,3 Khosro khajeh,4

Abstract


Introduction

Glioblastoma multiform (gbm) is the most common and aggressive form of primary brain cancer and has a dismal prognosis, with a 12- to 16-months median survival. current treatments for gbm including surgical resection, external beam radiation therapy, and chemotherapy are not successful in cancer suppression. epigenetic therapy and drug combination therapy are highly attention as two strong and hopeful strategies against aggressive solid tumors such as gmb. drug combination therapies play an increasingly central role in treatment of a wide variety of cancers since drug combinations have the potential to improve treatment response, minimize development of resistance or minimize adverse events. response surface methodology (rsm) is the most popular optimization method used within recent years. rsm consists of a group of mathematical and statistical techniques that can be used to define an optimum combination of different parameters.

Methods

Glioblastoma cell line -u251- was treated with four epi-drugs (including saha, 5-azacytidine, gsk-126, ptc-209) individually and cell survival ( ic50 ) was determined using the methyl-thiazolyl-tetrazolium ( mtt ) assay for each drug, then rsm was used to find the optimized concentration of epi- drugs in combination.

Results

The selected combination of rsm analysis showed lower doses of each epi-drugs with more efficient decrease of cell viability in u251 cell line.

Conclusion

This research recommends that rsm is a powerful method for optimizing drug concentration and improving for cancer treatment proposes.

Keywords

Rsm, epi-drug, drug combination