Abstract 532P
Background
Glioblastoma is the most common and aggressive type of primary brain tumor, with a high morbidity and mortality rate. Nitric oxide (NO) has been shown to have diverse effects on various cancers, including glioblastoma. Nitric oxide synthase (NOS) activation has been implicated in the growth and progression of glioblastoma. In this study, we investigated the effects of our novel two drugs HU-53 and HU-54, on the U87-MG cell line and a xenograft model of glioblastoma. Both drugs attenuate nitrative stress through different mechanisms.
Methods
NOD.CB17-Prkdc-scid/NCrHsd mice were used for the xenograft subcutaneous tumor model to evaluate the ability of HU-53 and HU-54 treatment regimens. Both treatments were given intraperitoneally. Tumor weight and volume were measured during the study. The experiments were also carried out on the human-derived U87-MG cells. Nitrite content was measured biochemically by Griess assay. Immunofluorescence and immunoblotting assessed nitrosative stress.
Results
We found that treatment with the combo-drug resulted in a significant decrease (P<0.0001) in cell viability and proliferation as compared to vehicle in the U87-MG cell line. The combo-drug also induced apoptosis as evidenced by increased caspase-3 activity. In addition, treatment with HU-53 and HU-54 resulted in a significant reduction (p<0.0001) in tumor growth in the xenograft model of glioblastoma, as demonstrated by decreased tumor volume and weight. Furthermore, we observed that the combo treatment resulted in a significant decrease in the level of nitrite content (p<0.02) and 3-Nitrotyrosine (a marker of nitrosative stress) which are important mediators of glioblastoma growth.
Conclusions
Our results suggest that targeting the nitrosative stress with HU-53 and HU-54 may be a promising therapeutic strategy for glioblastoma treatment.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The Hebrew University of Jerusalem.
Funding
The Hebrew University of Jerusalem, Israel.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
612P - Updated results from the multicenter phase II study of fruquintinib plus mFOLFOX6/FOLFIRI as first-line therapy in advanced metastatic colorectal cancer (mCRC)
Presenter: fuxiang zhou
Session: Poster session 10
613P - Effect of prior use of anti-VEGF agents on overall survival in patients with refractory metastatic colorectal cancer: A post-hoc analysis of the phase III SUNLIGHT trial
Presenter: Gerald Prager
Session: Poster session 10
614P - Effect of KRASG12 mutations on overall survival in patients with refractory metastatic colorectal cancer: A post-hoc analysis of the phase III SUNLIGHT trial
Presenter: Josep Tabernero
Session: Poster session 10
615P - The impacts of starting regorafenib dose on treatment outcomes in metastatic colorectal cancer
Presenter: Satoshi Yuki
Session: Poster session 10
616P - Sequential treatment with regorafenib (REG) and trifluridine/tipiracil (TAS) +/- bevacizumab (Bev) in refractory metastatic colorectal cancer (mCRC) in community clinical practice in the USA
Presenter: Tanios Bekaii-Saab
Session: Poster session 10
618P - Efficacy and safety of vactosertib and pembrolizumab combination in patients with previously treated microsatellite stable metastatic colorectal cancer
Presenter: Tae Won Kim
Session: Poster session 10
619P - Pelareorep + atezolizumab and chemotherapy in third-line (3L) metastatic colorectal cancer (mCRC) patients: Interim results from the GOBLET study
Presenter: Guy Ungerechts
Session: Poster session 10
620P - A phase II trial evaluating the activity of cabozantinib in pre-treated patients with metastatic colorectal cancer (mCRC): ABACO trial initial molecular data
Presenter: Giulia Martini
Session: Poster session 10
621P - The systemic proteome of consensus molecular subtypes from patients with RAS wild-type metastatic colorectal cancer: Analysis from the randomized phase II PanaMa (AIO KRK0212) trial
Presenter: Alexej Ballhausen
Session: Poster session 10