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.

机构信息

Department of Bioscience and Oral Diagnosis, Institute of Science and Technology, University of São Paulo State, Avenue Engenheiro Francisco José Longo, 777, São José dos Campos, São Paulo, 12245-000, Brazil.

Oral Medicine and Pathology Department, School of Dentistry, Universidad de Chile, Santiago, Chile.

出版信息

J Cancer Res Clin Oncol. 2024 Aug 18;150(8):390. doi: 10.1007/s00432-024-05924-x.

DOI:10.1007/s00432-024-05924-x

PMID:39154308

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11330948/

Abstract

OBJECTIVES

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

目的

化学预防可作为潜在恶性病变（PML）的治疗方法。本研究旨在评估青蒿素（ART）和顺铂（CSP）是否与体外口腔白斑（OL）和口腔鳞状细胞癌（OSCC）细胞系中的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能预防体内 OL 的进展。

方法

用 ART、CSP 和 ART+CSP 处理正常角质形成细胞（HaCat）、发育异常口腔细胞（DOK）和口腔鳞状细胞癌细胞（SCC-180）系，以分析细胞毒性、遗传毒性、细胞迁移和与凋亡和 ICD 相关的蛋白表达增加。此外，用 4NQO 诱导 41 只小鼠发生 OL，并用 ART 和 CSP 进行治疗，并对其舌组织进行组织学分析。

结果

体外，CSP 和 CSP+ART 表现出剂量依赖性细胞毒性，并降低了 SCC-180 的迁移。无处理方法具有遗传毒性，也未诱导与凋亡和 ICD 相关的蛋白表达；CSP 可显著降低 SCC-180 中高迁移率族蛋白 1（HMGB-1）蛋白的表达。体内，ART 和 CSP 治疗可延迟 OL 的进展；然而，到第 16 周时，只有 CSP 可预防向 OSCC 的进展。