The Chemotherapy Medication of Evodia lepta (Spreng). Merr. on the Viability of Tongue Cancer Cells Through the PD-L1/MMP14/HSPA5 Pathway.

IF 2.6 4区医学 Q3 ONCOLOGY

Cancer Management and Research Pub Date : 2025-08-12 eCollection Date: 2025-01-01 DOI:10.2147/CMAR.S533380

Jingkun Chen, Xiaohui Zheng, Xiaobing Wang, Ching-Feng Weng

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Abstract

Background: Oral tongue squamous cell carcinoma (OTSCC), the most prevalent oral malignancy, lacks effective treatments.

Objective: Evaluate Evodia lepta (E. lepta) as a potential OTSCC therapeutic.

Methods: Cell viability (CCK-8) and protein expression (Western blot) were assessed in OTSCC (CAL27, TCA8113) and 3T3 cells after 24h treatment with E. lepta or cisplatin.

Results: Cisplatin significantly reduced the viability in all cells (IC₅₀: 3T3 = 9.5 μM; CAL27/TCA8113 = 3.5 μM). E. lepta selectively targeted OTSCC cells (IC₅₀: CAL27 = 80 μg/mL; TCA8113 = 60 μg/mL) with no 3T3 toxicity. Protein expression analysis revealed that E. lepta downregulated GPX4, ADRM1, MMP14, PD-L1, and HSPA5 in both CAL27 and 3T3 cells. Interestingly, the expression of p17 exhibited divergent regulation between cell types. In contrast, cisplatin treatment upregulated GPX4 and downregulated MMP14, PD-L1, and HSPA5 in CAL27 cells, with p17 regulation opposing that observed with E. lepta.

Conclusion: E. lepta selectively induces ferroptosis through GPX4 and HSPA5 downregulation, demonstrating multi-target effects including proteostasis disruption (ADRM1), metastasis inhibition (MMP14), and immune evasion suppression (PD-L1). Its GPX4 suppression contrasts with cisplatin's upregulation, suggesting utility in cisplatin-resistant OTSCC. PD-L1 reduction implies immunotherapeutic potential, meriting further study.

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吴茱萸（春）的化疗用药。稳定。PD-L1/MMP14/HSPA5通路对舌癌细胞活力的影响

背景：口腔舌鳞癌（OTSCC）是最常见的口腔恶性肿瘤，缺乏有效的治疗。目的：评价吴茱萸（E. lepta）作为OTSCC的潜在治疗药物。方法：采用Western blot法检测麻霉或顺铂作用24h后OTSCC （CAL27、TCA8113）和3T3细胞的细胞活力（CCK-8）和蛋白表达情况。结果：顺铂显著降低各组细胞活力（IC50: 3T3 = 9.5 μM; CAL27/TCA8113 = 3.5 μM）。lepta选择性靶向OTSCC细胞（IC50: CAL27 = 80 μg/mL; TCA8113 = 60 μg/mL），无3T3毒性。蛋白表达分析显示，E. lepta在CAL27和3T3细胞中下调GPX4、ADRM1、MMP14、PD-L1和HSPA5。有趣的是，p17的表达在不同的细胞类型中表现出不同的调控。相比之下，顺铂治疗上调CAL27细胞中的GPX4，下调MMP14、PD-L1和HSPA5，而p17的调节与E. lepta相反。结论：lepta通过下调GPX4和HSPA5选择性诱导铁上坠，并表现出包括蛋白酶抑制（ADRM1）、转移抑制（MMP14）和免疫逃避抑制（PD-L1）在内的多靶点效应。GPX4的抑制作用与顺铂的上调作用形成对比，提示其在顺铂耐药OTSCC中的应用。PD-L1减少意味着免疫治疗潜力，值得进一步研究。

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来源期刊

Cancer Management and Research Medicine-Oncology

CiteScore

7.40

自引率

0.00%

发文量

448

审稿时长

16 weeks

期刊介绍： Cancer Management and Research is an international, peer reviewed, open access journal focusing on cancer research and the optimal use of preventative and integrated treatment interventions to achieve improved outcomes, enhanced survival, and quality of life for cancer patients. Specific topics covered in the journal include: ◦Epidemiology, detection and screening ◦Cellular research and biomarkers ◦Identification of biotargets and agents with novel mechanisms of action ◦Optimal clinical use of existing anticancer agents, including combination therapies ◦Radiation and surgery ◦Palliative care ◦Patient adherence, quality of life, satisfaction The journal welcomes submitted papers covering original research, basic science, clinical & epidemiological studies, reviews & evaluations, guidelines, expert opinion and commentary, and case series that shed novel insights on a disease or disease subtype.