目的:化学预防可以治疗潜在的恶性病变(PML)。我们旨在评估青蒿素(ART)和顺铂(CSP)是否与体外细胞凋亡和免疫原性细胞死亡(ICD)相关。使用口腔白斑(OL)和口腔鳞状细胞癌(OSCC)细胞系,以及这些化合物是否在体内阻止OL进展。
方法:正常角质形成细胞(HaCat),口腔发育不良细胞(DOK),和口腔鳞状细胞癌(SCC-180)细胞系用ART治疗,CSP,和ART+CSP来分析细胞毒性,遗传毒性,细胞迁移,与凋亡和ICD相关的蛋白表达增加。此外,使用4NQO用OL诱导41只小鼠,用ART和CSP治疗,对它们的舌头进行了组织学分析。
结果:体外,CSP和CSP+ART显示剂量依赖性细胞毒性和减少的SCC-180迁移。没有治疗是基因毒性的,未诱导与凋亡和ICD相关的蛋白表达;CSP显着降低了SCC-180中的高迁移率族蛋白盒1(HMGB-1)蛋白表达。在体内,ART和CSP治疗的OL进展延迟;然而,到第16周,只有CSP阻止了OSCC的进展。
结论:与ICD和细胞凋亡相关的蛋白表达没有随着治疗而增加,和CSP显示减少SCC-180中的免疫原性途径,同时减少细胞迁移。ART不能预防体内OL的恶性进展;尽管有明显的不良反应,但CSP确实如此。
OBJECTIVE: 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.
CONCLUSIONS: 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.