P04.92 Silencing Lis1 gene enhances the radiosensitivity and chemosensitivity of U87 glioblastoma cells grown in vitro

• Published in: Neuro-oncology (Charlottesville, Va.) Va.), 2018-09, Vol.20 (suppl_3), p.iii302-iii302
• Main Authors: Brehar, F M, Trusca, V G, Gafencu, A V, Petrescu, G E D, Sandu, A M, Amaireh, M, Gorgan, M R
• Format: Article
• Language: English
• Subjects: Poster Presentations
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/noy139.326

Abstract Background Our previous results showed that Lis1 gene is preferentially expressed in CD133+ glioblastoma cells and suggested a role of Lis1 in maintaining the CD133+ glioblastoma cell population. It is also known that CD133+ cells are resistant against radiation therapy and chemotherapy. Therefore, we tested if the Lis1 gene silencing could increase in vitro the radiosensitivity and chemosensitivity of U87 glioblastoma cells. Material and Methods Lis1 gene expression was silenced in U87 cells by stable transfection using specific shRNA plasmids. U87 cells having Lis1 gene silenced (shLis1 U87 cells) and control U87 cells were irradiated with a 25 Gy X-ray dose. U87 control and shLis U87 irradiated or non-irradiated cells, treated or not with 50 nM temozolomide were followed for their proliferative capacity for 100 hours in xCelligence RTCA instrument. Results Our results demonstrate that irradiated U87 cells have a higher proliferative capacity than irradiated shLis-U87 cells. Using the xCELLigence system, we showed that the proliferation rate of the control cell is significantly higher as compared to shLis1 U87 cells, and the biggest difference is obtained at 100 hours after exposure to 25 Gy (a cell index of approximately three times less for shLis1 U87 compared with control U87). The chemosensitivity experiments demonstrated important differences between control U87 cells and shLis1 U87 cells proliferation rate when cells were exposed to 50 nM temozolomide. The cell index of shLis1 U87 cells at 100 h was four times diminished as compared with control U87 cells. The increased radiosensitivity and chemosensitivity of shLis1 U87 culture compared with control U87 cells is that the Lis 1 gene silencing lead to a smaller number of CD133+ cells which are resistant to irradiation and temozolomide chemotherapy. Conclusion These results indicated that Lis1 gene silencing enhances the radiosensitivity and chemosensitivity of U87 cells glioblastoma cells in vitro. Our findings suggest that targeting Lis1 may become an important adjuvant therapy for standard radio- and chemotherapy in glioblastoma. Nevertheless, future in vitro and in vivo studies are necessary to confirm this hypothesis. This work was supported by a grant of the Romanian National Authority for Scientific Research, CNCS - UEFISCDI, project number PN-II-RU-TE-2012-3-0235 F.M.B., V.G.T. and A.V.G. contributed equally to the research done in this paper.