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Al-Ameer, H.J.* ; Zihlif, M.* ; Maslat, A.* ; Al-Awaida, W.J.* ; Ayyash, A.M.* ; Imraish, A.* ; Al-Qinna, N.* ; Al-Omari, T.* ; Al-Qaisi, T.* ; Al-Zyoud, W.* ; Alzubi, B.T.* ; Atoom, A.M.* ; Fattash, I.A.* ; Ambike, S. ; Goh, K.W.* ; Gushchina, Y.S.*

Targeting the proliferation of glioblastoma cells and enhancement of doxorubicin and temozolomide cytotoxicity through inhibition of PFKFB4 and HMOX1 genes with siRNAs.

Sci. Rep. 15, 17:27861 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Glioblastoma multiforme continues to be one of the most aggressive brain cancers, posing a serious health challenge, as it offers a median survival of only 15-23 months and a 5-year survival rate of less than 6%. Current treatments often prove inadequate, underscoring the urgency for new therapeutic strategies. This study investigated the potential of silencing the PFKFB4 and HMOX1 genes in U87-MG glioblastoma cells using small interfering RNAs (siRNAs), both alone and alongside the chemotherapeutic agents temozolomide (TMZ) and doxorubicin (DOX). Through MTT assays, qPCR, and wound healing techniques, we assessed cell viability, gene expression, and cell migration. Notably, siPFKFB4 enhanced DOX's cytotoxic effect, reducing its IC50 by six-fold, while having a milder impact with TMZ. When both siRNAs were combined with DOX, the IC50 decreased by two-fold without harming normal cells. Although siHMOX1 reduced cell migration, it only modestly affected cell proliferation with either DOX or TMZ. The gene expression analysis demonstrated that the siPFKFB4/DOX treatment led to an upregulation of pro-apoptotic genes such as DPYSL4, while simultaneously downregulating anti-apoptotic genes, including BCL-2 and PARP2. In contrast, the siHMOX1 combination influenced the expression of 14 genes, significantly enhancing the levels of CYLD, FAS, and CASP3, which are key promoters of apoptosis. In migration assays, siPFKFB4/DOX and siHMOX1/DOX reduced cell migration by 65 and 75%, respectively. These findings suggest that siPFKFB4 combined with DOX offers a promising pathway for GBM therapy, advocating further exploration into effective central nervous system drug delivery methods.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Doxorubicin ; Glioblastoma ; Hmox1 ; Human Health ; Pfkfb4 ; Temozolomide ; Sirna; Cancer Cells; Tumor-suppressor; Cathepsin S; Expression; Apoptosis; Metastasis; Growth; Resistance; Knockdown; Autophagy
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Zeitschrift Scientific Reports
Quellenangaben Band: 15, Heft: 1, Seiten: 17, Artikelnummer: 27861 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)
Förderungen This study was supported by the deanship of scientific research and graduate studies at Yarmouk University (Research Fund No.79/2021).