Chemosensitization of IκBα-overexpressing glioblastoma towards anti-cancer agents

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 I kappa B alpha gene, which is a cellular inhibitor of NF kappa B signaling pathways. The I kappa B alpha overexpressing U87MG cell line (U87-I kappa B alpha) was established by the G418 selection of I kappa B alpha transfected U87MG cells. The expression of I kappa B alpha 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-I kappa B alpha 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-I kappa B alpha cells. Results demonstrated the augmentation of the therapeutic potential of 5-FU and curcumin nanoparticles on I kappa B alpha overexpressed cells. Thus, this simple strategy offers the scope of using combination modules as a potential cancer therapeutic.