Prof Pablo Agustin Vargas , Dr. Luan César da Silva , Prof. Rogério Moraes Castilho
{"title":"利用 NFκB 抑制剂靶向破坏癌症干细胞，使口腔鳞状细胞癌对化疗敏感","authors":"Prof Pablo Agustin Vargas , Dr. Luan César da Silva , Prof. Rogério Moraes Castilho","doi":"10.1016/j.oooo.2024.04.048","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><p>Oral squamous cell carcinoma (OSCC) shows a limited response to current systemic treatments, and this resistance could be associated with cancer stem cells (CSC). NFκB is an activated pathway in several malignancies, including head and neck cancer. Here we evaluated the role of NFκB inhibitor on the behavior of CSC derived from OSCC.</p></div><div><h3>Material and methods</h3><p>Emetine was used as an NFκB inhibitor. CSC presence was assessed by tumorspheres, and the emetine IC<sub>50</sub> was determined in this specific cell population. Also, the CSC was quantified by the enzymatic activity of aldehyde dehydrogenases (ALDH) using flow cytometry. Immunofluorescence staining for phosphorylated protein p65 was used to identify the NFκB levels of tumor cells. Finally, OSCC cells were sensitized with emetine for 24 hours followed by administration of cisplatin (IC<sub>50</sub>).</p></div><div><h3>Results</h3><p>The IC<sub>50</sub> of emetine in CSC OSCC was 0.5μM. We then treated the OSCC cells with the emetine IC<sub>50</sub>, which showed a significant reduction of the ALDH population, while the NFκB pathway was inhibited. Further, emetine sensitized OSCC cells to cisplatin, resulting in a reduction of the IC<sub>50</sub> from 3.9μM to 1.3μM for SCC9.</p></div><div><h3>Conclusion</h3><p>Our results suggested that CSCs play an important role in tumor resistance to chemotherapy and highlight the disruption of these cells by the NFκB inhibition as a promisor target therapy.</p></div>","PeriodicalId":49010,"journal":{"name":"Oral Surgery Oral Medicine Oral Pathology Oral Radiology","volume":"138 2","pages":"Pages e44-e45"},"PeriodicalIF":2.0000,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Sensitizing oral squamous cell carcinoma to chemotherapy by targeted disruption of cancer stem cells using an NFκB inhibitor\",\"authors\":\"Prof Pablo Agustin Vargas , Dr. Luan César da Silva , Prof. Rogério Moraes Castilho\",\"doi\":\"10.1016/j.oooo.2024.04.048\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><p>Oral squamous cell carcinoma (OSCC) shows a limited response to current systemic treatments, and this resistance could be associated with cancer stem cells (CSC). NFκB is an activated pathway in several malignancies, including head and neck cancer. Here we evaluated the role of NFκB inhibitor on the behavior of CSC derived from OSCC.</p></div><div><h3>Material and methods</h3><p>Emetine was used as an NFκB inhibitor. CSC presence was assessed by tumorspheres, and the emetine IC<sub>50</sub> was determined in this specific cell population. Also, the CSC was quantified by the enzymatic activity of aldehyde dehydrogenases (ALDH) using flow cytometry. Immunofluorescence staining for phosphorylated protein p65 was used to identify the NFκB levels of tumor cells. Finally, OSCC cells were sensitized with emetine for 24 hours followed by administration of cisplatin (IC<sub>50</sub>).</p></div><div><h3>Results</h3><p>The IC<sub>50</sub> of emetine in CSC OSCC was 0.5μM. We then treated the OSCC cells with the emetine IC<sub>50</sub>, which showed a significant reduction of the ALDH population, while the NFκB pathway was inhibited. Further, emetine sensitized OSCC cells to cisplatin, resulting in a reduction of the IC<sub>50</sub> from 3.9μM to 1.3μM for SCC9.</p></div><div><h3>Conclusion</h3><p>Our results suggested that CSCs play an important role in tumor resistance to chemotherapy and highlight the disruption of these cells by the NFκB inhibition as a promisor target therapy.</p></div>\",\"PeriodicalId\":49010,\"journal\":{\"name\":\"Oral Surgery Oral Medicine Oral Pathology Oral Radiology\",\"volume\":\"138 2\",\"pages\":\"Pages e44-e45\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2024-07-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Oral Surgery Oral Medicine Oral Pathology Oral Radiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2212440324002256\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"DENTISTRY, ORAL SURGERY & MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oral Surgery Oral Medicine Oral Pathology Oral Radiology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2212440324002256","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
Sensitizing oral squamous cell carcinoma to chemotherapy by targeted disruption of cancer stem cells using an NFκB inhibitor
Introduction
Oral squamous cell carcinoma (OSCC) shows a limited response to current systemic treatments, and this resistance could be associated with cancer stem cells (CSC). NFκB is an activated pathway in several malignancies, including head and neck cancer. Here we evaluated the role of NFκB inhibitor on the behavior of CSC derived from OSCC.
Material and methods
Emetine was used as an NFκB inhibitor. CSC presence was assessed by tumorspheres, and the emetine IC<sub>50</sub> was determined in this specific cell population. Also, the CSC was quantified by the enzymatic activity of aldehyde dehydrogenases (ALDH) using flow cytometry. Immunofluorescence staining for phosphorylated protein p65 was used to identify the NFκB levels of tumor cells. Finally, OSCC cells were sensitized with emetine for 24 hours followed by administration of cisplatin (IC<sub>50</sub>).
Results
The IC<sub>50</sub> of emetine in CSC OSCC was 0.5μM. We then treated the OSCC cells with the emetine IC<sub>50</sub>, which showed a significant reduction of the ALDH population, while the NFκB pathway was inhibited. Further, emetine sensitized OSCC cells to cisplatin, resulting in a reduction of the IC<sub>50</sub> from 3.9μM to 1.3μM for SCC9.
Conclusion
Our results suggested that CSCs play an important role in tumor resistance to chemotherapy and highlight the disruption of these cells by the NFκB inhibition as a promisor target therapy.
期刊介绍：
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology is required reading for anyone in the fields of oral surgery, oral medicine, oral pathology, oral radiology or advanced general practice dentistry. It is the only major dental journal that provides a practical and complete overview of the medical and surgical techniques of dental practice in four areas. Topics covered include such current issues as dental implants, treatment of HIV-infected patients, and evaluation and treatment of TMJ disorders. The official publication for nine societies, the Journal is recommended for initial purchase in the Brandon Hill study, Selected List of Books and Journals for the Small Medical Library.
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