Targeting glioblastoma multiforme using a novel fusion protein comprising interleukin-13 and staphylococcal enterotoxin B in vitro.

Autor: Gholipour Z; Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran., Fooladi AAI; Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran. Electronic address: imanifouladi.a@gmail.com., Parivar K; Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran., Halabian R; Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Jazyk: angličtina
Zdroj: Toxicology in vitro : an international journal published in association with BIBRA [Toxicol In Vitro] 2023 Oct; Vol. 92, pp. 105651. Date of Electronic Publication: 2023 Jul 21.
DOI: 10.1016/j.tiv.2023.105651
Abstrakt: Targeting cell surface receptors with immunotoxins provides a novel, unique and highly potent treatment against cancers. A high expression of interleukin-13 (IL13) receptor α2 (IL13Rα2) has been reported in different types of cancers including glioblastoma multiforme (GBM). In this paper, to target IL13Rα2 on GBM cells, a fusion protein was generated comprising human IL13 and staphylococcal enterotoxin B (SEB), termed IL13-linker-SEB. The fusion protein was cloned into pET28a(+) and expressed in Escherichia coli strain BL21 (DE3); U251 (IL13Rα2-positive) and T98G (IL13Rα2-negative) GBM cell lines were employed and the functional activity of IL13-linker-SEB was evaluated by cell ELISA, cytotoxicity (MTT and LDH), apoptosis (flow cytometry and caspase-3 activity), adhesion, scratch and RT-PCR tests. SEB and chemotherapeutic drugs were employed to be compared to IL13-linker-SEB function. The IL13-linker-SEB exhibited higher binding affinity and cytotoxicity compared to SEB on U251 cells, although both recombinant proteins had shown similar behavior regarding T98G cells. Furthermore, the highest induction of apoptosis was observed in U251 cells treated with IL13-linker-SEB which was confirmed by Bax/Bcl-2 ratio. The expression of MMP2, MMP9 and VEGFR2 in U251 cells experienced a significant reduction after treatment with IL13-linker-SEB compared to SEB and T98G treated cells. The data showed that IL13-linker-SEB can be considered as a novel potential agent for GBM treatment; however, further research is needed to investigate the efficacy.
Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest.
(Copyright © 2023. Published by Elsevier Ltd.)
Databáze: MEDLINE
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