The role of resveratrol in the increase the sensitivity of glioblastoma cells and drug resistance through P-glycoprotein pathway and MAPK/MiR647/AKT signaling

Abstract

Glioblastoma multiforme is one of the most malignant types of brain tumors, this disease is somewhat resistant to treatment, one of the main causes of death from this disease is the resistance of cancer cells to chemotherapy drugs, which can lead to failure of chemotherapy. In order to overcome this problem, we focus on the effects of natural compounds with the ability to increase the sensitivity of cancer cells to chemotherapy drugs, so that with the help of these compounds, the stability and longevity of drugs in the cell and its function in the cell can be increased. Among these compounds is resveratrol, which was investigated in this study.

Materials and methods

U251 glioblastoma cell line was used in this study. First, the cells were cultured. Then, it was treated with the combination of resveratrol and temozolamide and its cytotoxic effect on the cells was determined using the MTT test, and in order to investigate the expression of 3Caspase-MAPK, MiR-647, Bax, Bcl-2 genes and their expression level. P-gp, MAPK, Bax, Bcl-2, 3Caspase were used by western blot test and qRT-PCR test.

Results

The results of this study showed that the combination of temozolamide and resveratrol significantly increases the expression of Caspase-3 and Bax and the level of apoptosis in temozolamide-resistant U251 cells with a significant difference (p<0.05). In addition, this combination of temozolamide and resveratrol can also decrease the expression of 647, MiR2MAPK, P-gp, Bcl with a significant difference (p<0.05).