Mechanisms of cell resistance in glioblastoma multiforme

Abstract

Glioblastoma multiforme is the most common brain tumor in adults. It is characterized by a rapid clinical course and extremely unfavorable prognosis. The etiology and the molecular pathogenetic mechanisms are not entirely clear yet. Active proliferation, resistance to apoptosis and high angiogenicity are basic factors limiting the effect of standard therapy.A significant problem is the resistance of glioblastoma cells to apoptosis induced by most of antitumor drugs and radiotherapy. The functional activity of several tumorsuppressor genes is inhibited. The antiapoptotic effect of the normal brain matrix and the altered expression of integrin aVb3 act as main regulators of angiogenesis, invasion and proliferation of glioblastoma cells.Therapeutic strategies are based on cellular and molecular mechanisms leading to: activation of apoptosis, inhibition of growth factors and receptors, and blocking of angiogenesis. Crucial moment in modern therapy is the activation of autophagy. Its effectiveness depends on the expression level of genes mTOR and MTMG. The most promising approach is the complex one combining surgery, radiotherapy and targeted molecular therapy directed simultaneously to different cellular pathogenetic mechanisms.

Perphenazine and prochlorperazine decrease glioblastoma U‑87 MG cell migration and invasion: Analysis of the ABCB1 and ABCG2 transporters, E‑cadherin, α‑tubulin and integrins (α3, α5, and β1) levels

“…In our study cells were incubated for 24 h before the western blot analysis, consequently 2 bands 60 and 80 kDa could be visible. We also evaluated the effect of perphenazine and prochlorperazine on wound closure, invasion and migration of human glioblastoma cell line, determined with the Transwell assay, since migrating cells at the marginal zones of GBM tumors are less sensitive to apoptosis, leading in consequence to the frequent recurrences (42). The wound-healing assay showed a time-dependent increase in wound area closure.…”

In Vitroeffects of Selenium on Human Glioblastoma Multiforme Cell Lines: A Preliminary Study

“…Th e development of drug resistance is a common condition in GBM. Th e most important problem with drugs is associated with those that cannot pass the blood-brain barrier 32 . Selenium can cross the blood-brain barrier and selenoprotein P is expressed in the brain 33 .…”