TY - JOUR

T1 - Glioblastoma Multiforme: Sensitivity to Antimicrobial Peptides LL-37 and PG-1, and Their Combination with Chemotherapy for Predicting the Overall Survival of Patients

AU - Chernov, A.N.

AU - Skliar, S.S.

AU - Kim, A.V.

AU - Tsapieva, A.

AU - Pyurveev, S.S.

AU - Filatenkova, T.A.

AU - Matsko, M.V.

AU - Ivanov, S.D.

AU - Shamova, O.V.

AU - Suvorov, A.N.

N1 - Export Date: 19 October 2024 Адрес для корреспонденции: Chernov, A.N.; World-Class Research Center “Center for Personalized Medicine”, Russian Federation; эл. почта: al.chernov@mail.ru Химические вещества/CAS: carboplatin, 41575-94-4; cisplatin, 15663-27-1, 26035-31-4, 96081-74-2; doxorubicin, 23214-92-8, 25316-40-9; etoposide, 33419-42-0, 433304-61-1; ropocamptide, 154947-66-7; temozolomide, 85622-93-1

PY - 2024/9/22

Y1 - 2024/9/22

N2 - Background/Objectives: Glioblastomas (GBMs) are the most malignant and intractable of all cancers, with an unfavorable clinical prognosis for affected patients. The objective was to analyze 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. Methods: The study was conducted on 27 GBM patients treated in the neurosurgical department of the Almazov Medical Research Centre (Saint Petersburg, Russia) from 2021 to 2024. The cytotoxic effects of chemotherapy, AMPs, and their combinations on brain tumor cells were assessed by an MTT assay using a 50% inhibitory concentration (IC50). Results: 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 anticancer effects were associated with a statistically significant increase in life expectancy and OS in GBM patients. These findings were confirmed by experiments on rats with C6 glioma, where the 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). Conclusions: Additionally, the combination of LL-37 and PG-1 with chemotherapy 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. © 2024 by the authors.

AB - Background/Objectives: Glioblastomas (GBMs) are the most malignant and intractable of all cancers, with an unfavorable clinical prognosis for affected patients. The objective was to analyze 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. Methods: The study was conducted on 27 GBM patients treated in the neurosurgical department of the Almazov Medical Research Centre (Saint Petersburg, Russia) from 2021 to 2024. The cytotoxic effects of chemotherapy, AMPs, and their combinations on brain tumor cells were assessed by an MTT assay using a 50% inhibitory concentration (IC50). Results: 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 anticancer effects were associated with a statistically significant increase in life expectancy and OS in GBM patients. These findings were confirmed by experiments on rats with C6 glioma, where the 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). Conclusions: Additionally, the combination of LL-37 and PG-1 with chemotherapy 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. © 2024 by the authors.

KW - chemotherapy drugs

KW - combinations of LL-37

KW - cytotoxicity

KW - glioblastoma

KW - LL-37

KW - overall survival of GBM patients

KW - PG-1

KW - PG-1 with chemotherapy

KW - antimicrobial peptide PG-1

KW - carboplatin

KW - cisplatin

KW - doxorubicin

KW - etoposide

KW - polypeptide antibiotic agent

KW - ropocamptide

KW - temozolomide

KW - unclassified drug

KW - animal experiment

KW - animal model

KW - Article

KW - chemotherapy

KW - clinical article

KW - controlled study

KW - histology

KW - human

KW - human cell

KW - human tissue

KW - IC50

KW - male

KW - MTT assay

KW - nonhuman

KW - nuclear magnetic resonance imaging

KW - overall survival

KW - rat

UR - https://www.mendeley.com/catalogue/7e0d8273-ef63-3529-9dc0-2447a75f5b4e/

U2 - 10.3390/pharmaceutics16091234

DO - 10.3390/pharmaceutics16091234

M3 - статья

C2 - 39339270

VL - 16

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 9

ER -