Abstract A31: Effects of Pin1 inhibition on tumorigenicity of glioblastoma multiforme

Abstract

Abstract Glioblastoma multiforme (GBM) is the most common and most aggressive type of primary brain tumor, accounting for 20% of all intracranial tumors. Current approaches in pursuit of treatment of GBM are not efficient in terms of increasing patient survivability or preventing recurrence after traditional treatments. Hunt for key molecules that might turn into drug targets have been rigorously continuing for GBM as well as other various types of tumors. Pin1, which was shown to be broadly overexpressed in various types of tumors, bears the potential to be one of the key molecular players in tumorigenesis. Molecular mechanisms underlying development and growth of the GBM, which is not completely curable by the means of chemotherapy, radiotherapy, and surgery, are not yet clearly identified. For the fact that the rate of treatment success of the agents in use against GBM is lower than acceptations, investigations for potential inhibitory target molecules for GBM development are increasing. Pin1 (peptidyl-prolyl cis/trans isomerase) is one of the molecules, recently identified and trying to be clarified during the search for potential target molecules on tumorigenicity. When compared with the health cells level of the Pin1 protein in many tumor cells like prostate, lung, breast and brain tumors is found to be extremely high. Recent studies aiming to identify Pin1's role on tumorigenicity have shown that increase in level of Pin1 in cells also led in increase of VEGF (Vascular Endothelial Growth Factor) as well. Our study aims to reveal the possible role for Pin1 as a therapeutic target and also inhibit the angiogenesis mechanism, which is common for tumors to develop, through inhibition of Pin1 U87 MG Glioblastoma cell line was used and Pin1 inhibition was performed via juglone, a Pin1 specific inhibitor molecule, and Pin1 siRNAs. Effects on Pin1 inhibition on tumorigenicity was assessed by MTT proliferation assay, wound healing assay to observe the migration characteristics, confocal microscopy technique to define morphological changes and apoptosis, and western blotting to define if angiogenesis related proteins are expressed. It is observed that Pin1 inhibition has affected and diminished the migration ability of U87 MG Glioblastoma cells. Changes on cell morphology and activation of apoptosis were also observed with reduced expression levels of angiogenesis related genes. We believe that, this study has a potential to reveal the effects of Pin1 inhibition as a therapeutic approach and will contribute to literature and clinical care in the future. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A31.