Chemosensitization of IκBα-overexpressing glioblastoma towards anti-cancer agents

Abstract

Burgeoning research on gene-directed therapeutics has significant translational scope to combat multidrug resistant glioblastoma when conventional anticancer drugs cease to work alone or in combination. In the present work, a novel strategy to sensitize drug resistant glioblastoma cells (U87MG) has been proposed by overexpressing the IκBα gene, which is a cellular inhibitor of NFκB signaling pathways. The IκBα overexpressing U87MG cell line (U87-IκBα) was established by the G418 selection of IκBα transfected U87MG cells. The expression of IκBα was studied by semi-quantitative RT PCR, real time PCR and Western blot analysis. The stable cells were found to be easily sensitized by the anticancer drug 5-fluorouracil (5-FU) and an unconventional therapeutic agent curcumin nanoparticles. Cell viability assays and flow cytometry-based cell cycle studies showed dose dependent differential effects of 5-FU on U87-IκBα and U87MG cells. The expression status of various cell cycle genes was examined by real time PCR analysis. Furthermore, water soluble curcumin nanoparticles (NPs) were synthesized in the presence of poly-L-lysine and BSA to sensitize U87-IκBα cells. Results demonstrated the augmentation of the therapeutic potential of 5-FU and curcumin nanoparticles on IκBα overexpressed cells. Thus, this simple strategy offers the scope of using combination modules as a potential cancer therapeutic.