Resveratrol inhibits glioblastoma cells and chemoresistance progression through blockade P-glycoprotein and targeting AKT/PTEN signaling pathway

Abstract

Malignant gliomas have been categorized as a debilitating class of brain tumors that are resistant to radiation and chemotherapeutic drugs, and have a poor prognosis. Hyper-activation of PI3K/AKT pathway and overexpression of p-glycoprotein transporter contributes to enhanced glioblastoma survival and chemoresistance. Resveratrol which possibly inhibits PI3K pathway, has been thus investigated for a potential therapeutic role in glioma. In the present study, the effect of resveratrol on human U87MG and doxorubicin-resistant glioblastoma cells (U87MG/DOX) survival evaluated by MTT. The ability of resveratrol to overcome doxorubicin resistance in glioblastoma cells was also explored with Rhodamines 123 uptake and ELISA assays. Resveratrol reduced cell survival in a PTEN and P53-dependent manner which was an effect associated with the inhibition of PI3K signaling pathway and via the activation of P-glycoprotein. Our finding showed that resveratrol, as a glioblastoma cell growth inhibitor and chemosensitizer, could be promising if used in the treatment of brain cancer. Resveratrol inhibits the progression of glioblastoma cells and reverses chemoresistance by upregulating PTEN, and suppressing AKT and P-glycoprotein. Targeting PTEN with resveratrol may offer a novel therapeutic approach for the chemo-sensitization of glioblastoma cells.

Keywords: Chemo-sensitization; Glioblastoma; P-glycoprotein; PI3K/AKT pathway.