Effects of the Combined Treatment with a G-Quadruplex-Stabilizing Ligand and Photon Beams on Glioblastoma Stem-like Cells: A Magnetic Resonance Study

International Journal of Molecular Sciences

卷:22

Valentina Pirota¹  Filippo Doria¹  Alice Triveri¹  Lucia Ricci-Vitiani²  Mariachiara Buccarelli²  Antonio Antoccia³  Francesco Berardinelli³  Roberto Pallini⁴  Quintino Giorgio D’Alessandris⁴  Alessandra Palma⁵  Antonella Rosi⁵  Sveva Grande⁵  Anna Maria Luciani⁵ 

[1] Department of Chemistry, University of Pavia, 27100 Pavia, Italy;

[2] Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy;

[3] Department of Science, University of Rome “Roma Tre” and INFN Sezione di Roma Tre, 00146 Rome, Italy;

[4] Institute of Neurosurgery, Fondazione IRCCS Policlinico Universitario A. Gemelli, 00168 Rome, Italy;

[5] National Centre for Innovative Technologies in Public Health, Istituto Superiore di Sanità, 00161 Rome, Italy;

关键词: glioblastoma;    stem cells;    metabolism;    magnetic resonance spectroscopy;    photon beams;    G4-quadruplex ligand;   

DOI  :  10.3390/ijms222312709

来源: DOAJ

【 摘 要 】

Glioblastoma multiforme is a malignant primary brain tumor with a poor prognosis and high rates of chemo-radiotherapy failure, mainly due to a small cell fraction with stem-like properties (GSCs). The mechanisms underlying GSC response to radiation need to be elucidated to enhance sensitivity to treatments and to develop new therapeutic strategies. In a previous study, two GSC lines, named line #1 and line #83, responded differently to carbon ions and photon beams, with the differences likely attributable to their own different metabolic fingerprint rather than to radiation type. Data from the literature showed the capability of RHPS4, a G-quadruplex stabilizing ligand, to sensitize the glioblastoma radioresistant U251MG cells to X-rays. The combined metabolic effect of ligand #190, a new RHPS4-derivative showing reduced cardiotoxicity, and a photon beam has been monitored by magnetic resonance (MR) spectroscopy for the two GSC lines, #1 and #83, to reveal whether a synergistic response occurs. MR spectra from both lines were affected by single and combined treatments, but the variations of the analysed metabolites were statistically significant mainly in line #1, without synergistic effects due to combination. The multivariate analysis of ten metabolites shows a separation between control and treated samples in line #1 regardless of treatment type, while separation was not detected in line #83.

【 授权许可】

Unknown