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Receptor-Tyrosine Kinase Inhibitor Ponatinib Inhibits Meningioma Growth In Vitro and In Vivo

Overview
Journal Cancers (Basel)
Publisher MDPI
Specialty Oncology
Date 2021 Dec 10
PMID 34885009
Citations 3
Authors
Affiliations
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Abstract

To date, there is no standard-of-care systemic therapy for the treatment of aggressive meningiomas. Receptor tyrosine kinases (RTK) are frequently expressed in aggressive meningiomas and are associated with poor survival. Ponatinib is a FDA- and EMA-approved RTK inhibitor and its efficacy in meningioma has not been studied so far. Therefore, we investigated ponatinib as a potential drug candidate against meningioma. Cell viability and cell proliferation of ponatinib-treated meningioma cells were assessed using crystal violet assay, manual counting and BrdU assay. Treated meningioma cell lines were subjected to flow cytometry to evaluate the effects on cell cycle and apoptosis. Meningioma-bearing mice were treated with ponatinib to examine antitumor effects in vivo. qPCR was performed to assess the mRNA levels of tyrosine kinase receptors after ponatinib treatment. Full-length cDNA sequencing was carried out to assess differential gene expression. IC50 values of ponatinib were between 171.2 and 341.9 nM in three meningioma cell lines. Ponatinib induced G0/G1 cell cycle arrest and subsequently led to an accumulation of cells in the subG1-phase. A significant induction of apoptosis was observed in vitro. In vivo, ponatinib inhibited meningioma growth by 72.6%. Mechanistically, this was associated with downregulation of PDGFRA/B and FLT3 mRNA levels, and mitochondrial dysfunction. Taken together, ponatinib is a promising candidate for targeted therapy in the treatment of aggressive meningioma.

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References
1.
Shankar G, Abedalthagafi M, Vaubel R, Merrill P, Nayyar N, Gill C . Germline and somatic BAP1 mutations in high-grade rhabdoid meningiomas. Neuro Oncol. 2017; 19(4):535-545. PMC: 5464371. DOI: 10.1093/neuonc/now235. View

2.
Abril J, de Heredia M, Gonzalez L, Cleries R, Nadal M, Condom E . Altered expression of 12S/MT-RNR1, MT-CO2/COX2, and MT-ATP6 mitochondrial genes in prostate cancer. Prostate. 2008; 68(10):1086-96. DOI: 10.1002/pros.20771. View

3.
Tabish T, Narayan R . Mitochondria-targeted graphene for advanced cancer therapeutics. Acta Biomater. 2021; 129:43-56. DOI: 10.1016/j.actbio.2021.04.054. View

4.
Ren M, Hong M, Liu G, Wang H, Patel V, Biddinger P . Novel FGFR inhibitor ponatinib suppresses the growth of non-small cell lung cancer cells overexpressing FGFR1. Oncol Rep. 2013; 29(6):2181-90. DOI: 10.3892/or.2013.2386. View

5.
Hirata E, Sahai E . Tumor Microenvironment and Differential Responses to Therapy. Cold Spring Harb Perspect Med. 2017; 7(7). PMC: 5495051. DOI: 10.1101/cshperspect.a026781. View