{"title":"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","authors":"Jingkun Chen, Xiaohui Zheng, Xiaobing Wang, Ching-Feng Weng","doi":"10.2147/CMAR.S533380","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Oral tongue squamous cell carcinoma (OTSCC), the most prevalent oral malignancy, lacks effective treatments.</p><p><strong>Objective: </strong>Evaluate Evodia lepta (<i>E.</i> <i>lepta</i>) as a potential OTSCC therapeutic.</p><p><strong>Methods: </strong>Cell viability (CCK-8) and protein expression (Western blot) were assessed in OTSCC (CAL27, TCA8113) and 3T3 cells after 24h treatment with <i>E. lepta</i> or cisplatin.</p><p><strong>Results: </strong>Cisplatin significantly reduced the viability in all cells (IC<sub>50</sub>: 3T3 = 9.5 μM; CAL27/TCA8113 = 3.5 μM). <i>E. lepta</i> selectively targeted OTSCC cells (IC<sub>50</sub>: CAL27 = 80 μg/mL; TCA8113 = 60 μg/mL) with no 3T3 toxicity. Protein expression analysis revealed that <i>E. lepta</i> 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 <i>E. lepta</i>.</p><p><strong>Conclusion: </strong><i>E. lepta</i> 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.</p>","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":"17 ","pages":"1613-1623"},"PeriodicalIF":2.6000,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357569/pdf/","citationCount":"0","resultStr":"{\"title\":\"The Chemotherapy Medication of <i>Evodia lepta</i> (Spreng). Merr. on the Viability of Tongue Cancer Cells Through the PD-L1/MMP14/HSPA5 Pathway.\",\"authors\":\"Jingkun Chen, Xiaohui Zheng, Xiaobing Wang, Ching-Feng Weng\",\"doi\":\"10.2147/CMAR.S533380\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Oral tongue squamous cell carcinoma (OTSCC), the most prevalent oral malignancy, lacks effective treatments.</p><p><strong>Objective: </strong>Evaluate Evodia lepta (<i>E.</i> <i>lepta</i>) as a potential OTSCC therapeutic.</p><p><strong>Methods: </strong>Cell viability (CCK-8) and protein expression (Western blot) were assessed in OTSCC (CAL27, TCA8113) and 3T3 cells after 24h treatment with <i>E. lepta</i> or cisplatin.</p><p><strong>Results: </strong>Cisplatin significantly reduced the viability in all cells (IC<sub>50</sub>: 3T3 = 9.5 μM; CAL27/TCA8113 = 3.5 μM). <i>E. lepta</i> selectively targeted OTSCC cells (IC<sub>50</sub>: CAL27 = 80 μg/mL; TCA8113 = 60 μg/mL) with no 3T3 toxicity. Protein expression analysis revealed that <i>E. lepta</i> 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 <i>E. lepta</i>.</p><p><strong>Conclusion: </strong><i>E. lepta</i> 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.</p>\",\"PeriodicalId\":9479,\"journal\":{\"name\":\"Cancer Management and Research\",\"volume\":\"17 \",\"pages\":\"1613-1623\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-08-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357569/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Management and Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/CMAR.S533380\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Management and Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/CMAR.S533380","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
The Chemotherapy Medication of Evodia lepta (Spreng). Merr. on the Viability of Tongue Cancer Cells Through the PD-L1/MMP14/HSPA5 Pathway.
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.
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.
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