Exploring the “Cascade Effect” of AEBSF on Reduced Glioblastoma Proliferation

Abstract

Glioblastomas (GBMs) are one of the deadliest cancers, and yet still lack treatment. In this study, serine protease inhibitor AEBSF is shown to decrease GBM vi-ability and proliferation through a series of intertwined steps. By decreasing the expres-sion of ATP6V1A--the first step of the “cascade effect”--AEBSF creates an unfavorable environment for protease activity. Such “unfavorability” is proven by a decline in expres-sion of proteases MMP9 and ELANE upon GBM treatment with AEBSF. Increasingly higher concentrations of AEBSF are shown to decrease the percentage of cell viability, proliferation, and metastasis. This is explained through biological process enrichment analyses, which indicate that MMP9 and ELANE play a role in the disassembly of the extracellular protein network. This disassembly of the extracellular environment enables tumorigenic spread and viability. The results of the viability and proliferation assays, in combination with those of the indirect ELISAs, enrichment analyses, and scratch assays, underscore an intricate and profound sequence of events that constitute the “cascade effect”.