多形性胶质母细胞瘤:对抗菌肽 LL-37 和 PG-1 的敏感性,以及它们与化疗的组合用于预测患者的总体生存率。
Glioblastoma Multiforme: Sensitivity to Antimicrobial Peptides LL-37 and PG-1, and Their Combination with Chemotherapy for Predicting the Overall Survival of Patients.
发表日期:2024 Sep 22
作者:
Alexander N Chernov, Sofia S Skliar, Alexander V Kim, Anna Tsapieva, Sarng S Pyurveev, Tatiana A Filatenkova, Marina V Matsko, Sergey D Ivanov, Olga V Shamova, Alexander N Suvorov
来源:
Pharmaceutics
摘要:
背景/目标:胶质母细胞瘤(GBM)是所有癌症中最恶性和最难治的,受影响患者的临床预后不佳。目的是分析 GBM 细胞对抗菌肽 (AMP)、抗菌肽 (LL-37) 和 protegrin-1 (PG-1) 的敏感性,无论是单独使用还是与化疗联合使用,以预测 GBM 细胞的总生存期 (OS)。患者。方法:该研究对 2021 年至 2024 年在阿尔马佐夫医学研究中心(俄罗斯圣彼得堡)神经外科接受治疗的 27 名 GBM 患者进行。通过以下方法评估化疗、AMP 及其组合对脑肿瘤细胞的细胞毒性作用:使用 50% 抑制浓度 (IC50) 的 MTT 测定。结果:在患者GBM细胞中,LL-37和PG-1表现出很强的抗癌作用,超过化疗药物。这些 LL-37 和 PG-1 抗癌作用与 GBM 患者预期寿命和 OS 的统计显着增加相关。这些发现得到了 C6 神经胶质瘤大鼠实验的证实,鼻内注射 LL-37 (300 μM) 和 PG-1 (600 μM) 使动物的预期寿命分别延长至 69 天和 55 天,而 24对照组的天数(HR = 4.139,p = 0.0005;HR = 2.542,p = 0.0759)。结论:此外,LL-37 和 PG-1 与化疗药物的组合表明,GBM 细胞中 LL-37 与顺铂(截止值 > 800 μM)的高 IC50 与预期寿命延长相关(19 个月与 5 个月, GBM 患者的 HR = 4.708,p = 0.0101) 和 OS。这些组合可用于未来 GBM 治疗。
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.