Exosomes released from U۸۷ glioma cells treated with ۵-fluorouracil produce apoptosis in naïve U۸۷ cells

Glioblastoma multiforme (GBM) is the most prevalent and fatal malignancy of the CNS, that still lacks a definitive cure. The process of intercellular communication involves exosomes in the tumor microenvironment, which transport a variety of biomolecules. These exosomes play a crucial role in tumor development, differentiation, spread, and resistance to cancer treatments. Recent research has demonstrated their significant impact on immune cells. Due to their unique structure and functions, exosomes have the potential to provide a deeper understanding of tumor mechanisms. Furthermore, they can be utilized as markers for diagnosis/forecasting and as therapeutic agents to specifically target aggressive tumor cells, such as in the case of glioblastomas. In our previous study, we showed, for the first time, that the treatment of naïve U۸۷ cells with TMZ and curcumin is able to alter the composition of constituents of their released exosomes (Exo) in a way that makes them of anti-cancer properties. In this study, we treated naïve U۸۷ cells with ۵-FU to examine how ۵-FU can alter the content of their released Exo and also the pro-apoptotic function of these Exo (۵-FU-Exo). Exosomes were extracted by employing a centrifugation kit and their properties were determined through DLS, SEM, TEM, and Western blot analysis. The quantities of exosomal BDNF and TNF-α were quantified. Untreated U۸۷ cells were exposed to the isolated exosomes, and the impact on apoptosis-associated proteins HSP۲۷, HSP۷۰, HSP۹۰, and P۵۳ was evaluated. ۵-FU could not alter the level of TNF-α but caused a significant upregulation of BDNF and therefore an elevated exosomal TNF-α/BDNF ratio. ۵-FU-Exo could accelerate the apoptotic rate of naïve U۸۷ cells to an extent comparable to ۵-FU. Furthermore, ۵-FU-Exo could upregulate the expression of p۵۳ while downregulate the expression of HSP۷۰, HSP۹۰, and HSP۲۷, that may be attributed to their elevated TNF-α/BDNF ratio. Further mechanistic studies and also examination of exosomal content is required to elucidate the mechanism of action of these manipulated Exo. Our studies suggest the Exo separated from anti-cancer agent-treated cancer cells as a novel strategy for cancer treatment.

کلیدواژه ها:

Glioblastoma multiforme ، exosome ، ۵-fluorouracil ، TNF-α ، BDNF