青蒿素和顺铂对口腔白斑恶性进展的影响。体外和体内研究。
Effects of artemisinin and cisplatin on the malignant progression of oral leukoplakia. In vitro and in vivo study.
发表日期:2024 Aug 18
作者:
Mateus José Dutra, Isabella Souza Malta, Maria Leticia de Almeida Lança, Luana Marotta Reis de Vasconcellos, Daniela Adorno-Farias, José Antonio Jara, Estela Kaminagakura
来源:
Cellular & Molecular Immunology
摘要:
化学预防可以治疗潜在的恶性病变(PML)。我们的目的是使用口腔白斑 (OL) 和口腔鳞状细胞癌 (OSCC) 细胞系,在体外评估青蒿素 (ART) 和顺铂 (CSP) 是否与细胞凋亡和免疫原性细胞死亡 (ICD) 相关,以及这些化合物是否可以预防体内 OL 进展。用 ART、CSP 和 ART CSP 处理正常角质形成细胞 (HaCat)、发育不良口腔细胞 (DOK) 和口腔鳞状细胞癌 (SCC-180) 细胞系,分析细胞毒性、基因毒性、细胞迁移和与细胞凋亡和 ICD 相关的蛋白质表达增加。此外,41 只小鼠使用 4NQO 诱导 OL,接受 ART 和 CSP 处理,并对它们的舌头进行组织学分析。在体外,CSP 和 CSP ART 显示出剂量依赖性细胞毒性并减少 SCC-180 迁移。没有任何治疗具有遗传毒性,也没有诱导与细胞凋亡和 ICD 相关的蛋白质表达; CSP 显着降低了 SCC-180 中高迁移率组 box-1 (HMGB-1) 蛋白的表达。在体内,ART 和 CSP 治疗延迟了 OL 的进展;然而,到了第 16 周,只有 CSP 阻止了向 OSCC 的进展。与 ICD 和细胞凋亡相关的蛋白质表达并未随着治疗而增加,并且 CSP 被证明可以减少 SCC-180 中的免疫原性途径,同时减少细胞迁移。 ART并不能阻止OL体内的恶性进展;尽管有明显的不利影响,CSP 仍然做到了。© 2024。作者。
Chemoprevention can be a treatment for potentially malignant lesions (PMLs). We aimed to evaluate whether artemisinin (ART) and cisplatin (CSP) are associated with apoptosis and immunogenic cell death (ICD) in vitro, using oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) cell lines, and whether these compounds prevent OL progression in vivo.Normal keratinocytes (HaCat), Dysplastic oral cells (DOK), and oral squamous cell carcinoma (SCC-180) cell lines were treated with ART, CSP, and ART + CSP to analyze cytotoxicity, genotoxicity, cell migration, and increased expression of proteins related to apoptosis and ICD. Additionally, 41 mice were induced with OL using 4NQO, treated with ART and CSP, and their tongues were histologically analyzed.In vitro, CSP and CSP + ART showed dose-dependent cytotoxicity and reduced SCC-180 migration. No treatment was genotoxic, and none induced expression of proteins related to apoptosis and ICD; CSP considerably reduced High-mobility group box-1 (HMGB-1) protein expression in SCC-180. In vivo, there was a delay in OL progression with ART and CSP treatment; however, by the 16th week, only CSP prevented progression to OSCC.Expression of proteins related to ICD and apoptosis did not increase with treatments, and CSP was shown to reduce immunogenic pathways in SCC-180, while reducing cell migration. ART did not prevent the malignant progression of OL in vivo; CSP did despite significant adverse effects.© 2024. The Author(s).