Signal transduction molecule patterns indicating potential glioblastoma therapy approaches

Maria Linda Cruceru,¹ Ana-Maria Enciu,^1,2,7 Adrian Claudiu Popa,^1,3 Radu Albulescu,^2,4,7 Monica Neagu,^2,7 Cristiana Pistol Tanase,^2,7 Stefan N Constantinescu<sup>5–7

1</sup>Carol Davila University of Medicine and Pharmacy, Department of Cellular and Molecular Medicine, Bucharest, Romania; ²Victor Babes National Institute of Pathology, Bucharest, Romania; ³Army Centre for Medical Research, Bucharest, Romania; ⁴National Institute for Chemical Pharmaceutical R&D, Bucharest, Romania; ⁵de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; ⁶Ludwig Institute for Cancer Research, Brussels, Belgium; ⁷Operational Sectorial Programme for Competitive Economic Growth Canbioprot at Victor Babes National Institute of Pathology, Bucharest, Romania

Purpose: The expression of an array of signaling molecules, along with the assessment of real-time cell proliferation, has been performed in U87 glioma cell line and in patients’ glioblastoma established cell cultures in order to provide a better understanding of cellular and molecular events involved in glioblastoma pathogenesis. Experimental therapy was performed using a phosphatydylinositol-3´-kinase (PI3K) inhibitor.
Patients and methods: xMAP technology was employed to assess expression levels of several signal transduction molecules and real-time xCELLigence platform for cell behavior.
Results: PI3K inhibition induced the most significant effects on global signaling pathways in patient-derived cell cultures, especially on members of the mitogen-activated protein-kinase family, P70S6 serine-threonine kinase, and cAMP response element-binding protein expression and further prevented tumor cell proliferation.
Conclusion: The PI3K pathway might be a prime target for glioblastoma treatment.

Keywords: personalized medicine, PI3K inhibitor, targeted therapy, xCELLigence, xMAP analysis