Al's Comment:
Interesting study - but it is only in the test tube. We follow Aspirin in the virtual trial but nobody has recorded it - I know many people must be taking it long term for heart protection - they just aren't recording it. If you are in the virtual trial and take long term Aspirin , please go back and post an update so we can see if it helps!
Posted on: 08/27/2018
World Neurosurg. 2018 Aug 22. pii: S1878-8750(18)31863-1. doi: 10.1016/j.wneu.2018.08.080. [Epub ahead of print]
Aspirin affects tumor angiogenesis and sensitizes human glioblastoma endothelial cells to temozolomide, bevacizumab, and sunitinib impairing VEGF-related signaling.
Navone SE1, Guarnaccia L1, Cordiglieri C2, Crisà FM1, Caroli M1, Locatelli M1, Schisano L1, Rampini P1, Miozzo M3, La Verde N4, Riboni L5, Campanella R1, Marfia G6.
Author information:
1. Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Italy.
2. Istituto Nazionale di Genetica Molecolare "Romeo ed Enrica Invernizzi," Milan, Italy.
3. Division of Pathology, Department of Pathophysiology and Transplantation, University of Milan, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
4. Oncology Unit, Fatebenefratelli and Oftalmico Hospital, Milan, Italy.
5. Department of Medical Biotechnology and Translational Medicine, LITA-Segrate, University of Milan, Milan, Italy.
6. Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Italy. Electronic address: giovanni.marfia@unimi.it.
Abstract
BACKGROUND:
Glioblastoma (GBM) is the most common and fatal human brain tumor, with the worst prognosis. The aberrant microenvironment, prompted by the activation of pro-angiogenic mediators, as hypoxia-inducible-factor (HIF-1a), vascular endothelial growth factor (VEGF) and their downstream effectors, sustain GBM malignancy. Pro-angiogenic signaling represent an attractive chemotherapeutic target. Recent evidence suggests a therapeutic benefit from aspirin (ASA) intake in reducing risk and cancer progression.
METHODS:
In the present study, human primary GBM-endothelial cells (GBM-ECs) were used to ascertain whether ASA could inhibit angiogenesis and improve cell sensitivity to drugs. The impact of ASA was observed by measuring cell viability, tube-like structure formation, migration, VEGF production, and proliferative, pro-angiogenic and apoptotic modulators expression, as HIF-1a/VEGF/VEGFR-1/VEGFR-2, RAS/MEK/ERK, PI3K/AKT signaling axis and BAX/BCL-2 ratio. Furthermore, we evaluated the effect of ASA alone or in combination with Temozolomide (TMZ), Bevacizumab (BEV) and Sunitinib (SUN).
RESULTS:
Our data reported that ASA affected GBM-EC viability, tube-like structure formation, cell migration and VEGF releasing in a dose-dependent manner, and that combined treatments with TMZ, BEV and SUN synergized to counteract pro-angiogenic cell ability. mRNA expression analysis displayed a marked effect of ASA in reducing VEGF, VEGFR-1, HIF-1a, RAS, MEK, AKT and BCL-2, as well a combined anti-cancer effect of ASA together with TMZ, BEV and SUN. Levels of HIF-1a, VEGFR-2, BAX and BCL-2 protein expression confirmed a positive trend.
CONCLUSION:
Aspirin and anti-angiogenic therapies showed synergetic anticancer efficacy in human primary GBM-ECs. Thus, combine conventional chemotherapy with ASA may offer a new strategy to counteract tumor malignancy.
Copyright © 2018. Published by Elsevier Inc.
PMID: 30144594
Click HERE to return to brain tumor news headlines.
