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伊维菌素与地塞米松联合用药可诱导SUP-B15细胞系凋亡。

Ivermectin and dexamethasone combination induces apoptosis in SUP-B15 cell line.

作者信息

Siregar Olga R, Wahyuni Arlinda S, Pasaribu Ayodhia P, Edianto Deri, Ugrasena I Dg, Amelia Rina, Lubis Inke Nd, Rusda Muhammad

机构信息

Department of Pediatrics, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia.

Department of Community Medicine, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia.

出版信息

Narra J. 2025 Aug;5(2):e1975. doi: 10.52225/narra.v5i2.1975. Epub 2025 Apr 24.

Abstract

The development of glucocorticoid resistance has complicated the management of acute lymphoblastic leukemia (ALL), leading to increased mortality rates. Ivermectin, a low-cost and well-established anthelmintic, exhibits anticancer potential and may enhance glucocorticoid toxicity in ALL, offering a possible strategy to overcome resistance. The aim of this study was to evaluate the apoptotic effect of combining ivermectin with dexamethasone in ALL. ALL SUP-B15 cells were cultured under standard conditions before treatment with dexamethasone (200 nM) alone or combined with ivermectin (5, 10, and 20 µM), with an untreated group serving as the control. Cytotoxicity was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay by measuring cell viability and inhibition. Apoptosis was evaluated through BAX, BCL-2, and CASP3 gene expression analysis using reverse transcription-polymerase chain reaction (RT-PCR). The findings revealed that the combination of ivermectin and dexamethasone was superior in the repression of ALL cell viability compared to control (<0.001). The combination of dexamethasone 200 nM + ivermectin 20 μM demonstrated the most significant cell inhibition of 38.16±0.04% (<0.001) and produced the lowest cell viability of 61.84±0.05% (<0.001). Moreover, the combination of dexamethasone 200 nM + ivermectin 20 μM demonstrated superior upregulations of (<0.001) and (<0.001). In conclusion, the addition of ivermectin (5 µM) to dexamethasone regimen (200 nM) increases its cytotoxic and apoptotic activities against SUP-B15 cell line as observed by the and upregulation. Studies to confirm the enhanced anticancer activity by this combination by observing the protein levels and animal studies are warranted.

摘要

糖皮质激素耐药性的出现使急性淋巴细胞白血病(ALL)的治疗变得复杂,导致死亡率上升。伊维菌素是一种低成本且成熟的驱虫药,具有抗癌潜力,可能增强ALL中糖皮质激素的毒性,为克服耐药性提供了一种可能的策略。本研究的目的是评估伊维菌素与地塞米松联合使用对ALL的凋亡作用。ALL SUP - B15细胞在标准条件下培养,然后分别用单独的地塞米松(200 nM)或与伊维菌素(5、10和20 μM)联合处理,未处理组作为对照。使用3 -(4,5 - 二甲基噻唑 - 2 - 基)- 2,5 - 二苯基四氮唑溴盐(MTT)法通过测量细胞活力和抑制率来评估细胞毒性。通过逆转录 - 聚合酶链反应(RT - PCR)分析BAX、BCL - 2和CASP3基因表达来评估凋亡情况。研究结果显示,与对照组相比,伊维菌素和地塞米松联合使用在抑制ALL细胞活力方面更具优势(<0.001)。200 nM地塞米松 + 20 μM伊维菌素的组合表现出最显著的细胞抑制率,为38.16±0.04%(<0.001),且细胞活力最低,为61.84±0.05%(<0.001)。此外,200 nM地塞米松 + 20 μM伊维菌素的组合表现出BAX(<0.001)和CASP3(<0.001)的上调更显著。总之,如BAX和CASP3上调所观察到的,在200 nM地塞米松方案中添加5 μM伊维菌素可增加其对SUP - B15细胞系的细胞毒性和凋亡活性。有必要通过观察蛋白质水平和动物研究来证实这种联合用药增强抗癌活性的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13d4/12425513/5d8c74855da0/NarraJ-5-e1975-g001.jpg

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