Valproic acid-induced amphiregulin secretion confers resistance to temozolomide treatment in human glioma cells

BMC Cancer
Jui-Chieh ChenJen-Tsung Yang

Abstract

Glioblastoma multiforme (GBM) is the most severe type of primary brain tumor with a high mortality rate. Although extensive treatments for GBM, including resection, irradiation, chemotherapy and immunotherapy, have been tried, the prognosis is still poor. Temozolomide (TMZ), an alkylating agent, is a front-line chemotherapeutic drug for the clinical treatment of GBM; however, its effects are very limited because of the chemoresistance. Valproic acid (VPA), an antiepileptic agent with histone deacetylase inhibitor activity, has been shown to have synergistic effects with TMZ against GBM. The mechanism of action of VPA on TMZ combination therapy is still unclear. Accumulating evidence has shown that secreted proteins are responsible for the cross talking among cells in the tumor microenvironment, which may play a critical role in the regulation of drug responses. To understand the effect of VPA on secreted proteins in GBM cells, we first used the antibody array to analyze the cell culture supernatant from VPA-treated and untreated GBM cells. The results were further confirmed by lentivirus-mediated knockdown and exogenous recombinant administration. Our results showed that amphiregulin (AR) was highly secreted in VPA-treated cell...Continue Reading

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Citations

Sep 6, 2019·International Journal of Oncology·Ming-Ju HsiehJui-Chieh Chen
Apr 4, 2020·Neoplasia : an International Journal for Oncology Research·Patpicha ArunsanWannaporn Ittiprasert
Nov 5, 2020·Pharmacology & Therapeutics·Elena KunadisChristina Piperi
Aug 8, 2021·International Journal of Molecular Sciences·Qiong WuArnold B Etame

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Methods Mentioned

BETA
surgical resection
antibody array technology
antibody array
protein assay
electrophoresis
X-ray
PCR
xenograft
flow cytometry
antibody

Software Mentioned

iQ5 Optical System
GeneTools

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