PreprintArticleVersion 1This version is not peer-reviewed
Glioblastoma Multiforme: Sensitivity to Antimicrobial Peptides LL-37, PG-1 and Its Combinations with Chemotherapy for Prediction of Overall Survival of the Patients
Version 1
: Received: 2 August 2024 / Approved: 3 August 2024 / Online: 5 August 2024 (03:04:53 CEST)
How to cite:
Chernov, A. N.; Skliar, S. S.; Kim, A. V.; Tsapieva, A.; Pyurveev, S. S.; Filatenkova, T. A.; Matsko, M. V.; Ivanov, S. D.; Shamova, O. V.; Suvorov, A. N. Glioblastoma Multiforme: Sensitivity to Antimicrobial Peptides LL-37, PG-1 and Its Combinations with Chemotherapy for Prediction of Overall Survival of the Patients. Preprints2024, 2024080221. https://doi.org/10.20944/preprints202408.0221.v1
Chernov, A. N.; Skliar, S. S.; Kim, A. V.; Tsapieva, A.; Pyurveev, S. S.; Filatenkova, T. A.; Matsko, M. V.; Ivanov, S. D.; Shamova, O. V.; Suvorov, A. N. Glioblastoma Multiforme: Sensitivity to Antimicrobial Peptides LL-37, PG-1 and Its Combinations with Chemotherapy for Prediction of Overall Survival of the Patients. Preprints 2024, 2024080221. https://doi.org/10.20944/preprints202408.0221.v1
Chernov, A. N.; Skliar, S. S.; Kim, A. V.; Tsapieva, A.; Pyurveev, S. S.; Filatenkova, T. A.; Matsko, M. V.; Ivanov, S. D.; Shamova, O. V.; Suvorov, A. N. Glioblastoma Multiforme: Sensitivity to Antimicrobial Peptides LL-37, PG-1 and Its Combinations with Chemotherapy for Prediction of Overall Survival of the Patients. Preprints2024, 2024080221. https://doi.org/10.20944/preprints202408.0221.v1
APA Style
Chernov, A. N., Skliar, S. S., Kim, A. V., Tsapieva, A., Pyurveev, S. S., Filatenkova, T. A., Matsko, M. V., Ivanov, S. D., Shamova, O. V., & Suvorov, A. N. (2024). Glioblastoma Multiforme: Sensitivity to Antimicrobial Peptides LL-37, PG-1 and Its Combinations with Chemotherapy for Prediction of Overall Survival of the Patients. Preprints. https://doi.org/10.20944/preprints202408.0221.v1
Chicago/Turabian Style
Chernov, A. N., Olga V. Shamova and Alexander N Suvorov. 2024 "Glioblastoma Multiforme: Sensitivity to Antimicrobial Peptides LL-37, PG-1 and Its Combinations with Chemotherapy for Prediction of Overall Survival of the Patients" Preprints. https://doi.org/10.20944/preprints202408.0221.v1
Abstract
Glioblastomas (GBMs) are the most malignant and intractable of all cancers, with an unfavourable clinical prognosis for affected patients. The objective was analysis the sensitivity of GBM cells to the antimicrobial peptides (AMPs) cathelicidin (LL-37) and protegrin-1 (PG-1), both alone and in combination with chemotherapy, to predict overall survival (OS) in the patients. The study was conducted on 27 GBM patients treated in the neurosurgical departments of the Almazov Medical Research Centre (Saint-Petersburg, Russia) from 2021 to 2024. The cytotoxic effects of chemo-therapy, AMPs and their combinations on brain tumor cells were assessed by MTT assay using 50%-inhibitory concentration (IC50). In GBM cells from the patients, LL-37 and PG-1 exhibited strong anticancer effects, surpassing those of chemotherapy drugs. These LL-37 and PG-1 anti-cancer effects were associated with a statistically significant increase in life expectancy and OS in GBM patients. These findings were confirmed by the experiments on rats with C6 glioma, where intranasal administration of LL-37 (300 μM) and PG-1 (600 μM) increased the life expectancy of the animals to 69 and 55 days, respectively, compared to 24 days in the control group (HR=4.139, p=0.0005; HR=2.542, p=0.0759). Additionally, the combination of LL-37 and PG-1 with chemo-therapy drugs showed that a high IC50 of LL-37 with cisplatin (cutoff >800 μM) in GBM cells was associated with increased life expectancy (19 vs 5 months, HR=4.708, p=0.0101) and OS in GBM patients. These combinations could be used in future GBM treatments.
Keywords
glioblastoma; LL-37; PG-1; cytotoxicity; chemotherapy drugs; combinations of LL-37, PG-1 with chemotherapy; overall survival of the GBM patients
Subject
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.