Sensitizing oral squamous cell carcinoma to chemotherapy by targeted disruption of cancer stem cells using an NFκB inhibitor

IF 2 3区医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE

Oral Surgery Oral Medicine Oral Pathology Oral Radiology Pub Date : 2024-07-13 DOI:10.1016/j.oooo.2024.04.048

Prof Pablo Agustin Vargas , Dr. Luan César da Silva , Prof. Rogério Moraes Castilho

{"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":null,"pages":null},"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}

引用次数: 0

Abstract

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.

查看原文本刊更多论文

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

导言口腔鳞状细胞癌（OSCC）对目前的系统治疗反应有限，这种抗药性可能与癌症干细胞（CSC）有关。NFκB是包括头颈癌在内的多种恶性肿瘤的激活通路。在此，我们评估了NFκB抑制剂对来自OSCC的CSC行为的作用。通过肿瘤球评估CSC的存在，并确定这一特定细胞群中依美汀的IC<sub>50</sub>。此外，还利用流式细胞术通过醛脱氢酶（ALDH）的酶活性对 CSC 进行了量化。磷酸化蛋白 p65 的免疫荧光染色用于确定肿瘤细胞的 NFκB 水平。最后，用依美汀增敏 OSCC 细胞 24 小时，然后施用顺铂（IC<sub>50</sub>）。结果依美汀在 CSC OSCC 中的 IC<sub>50</sub> 为 0.5μM。然后，我们用依美汀 IC<sub>50</sub> 处理 OSCC 细胞，结果显示 ALDH 数量显著减少，而 NFκB 通路受到抑制。此外，依美汀还能使 OSCC 细胞对顺铂敏感，从而使 SCC9 的 IC<sub>50</sub> 从 3.9μM 降至 1.3μM。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Oral Surgery Oral Medicine Oral Pathology Oral Radiology DENTISTRY, ORAL SURGERY & MEDICINE-

CiteScore

3.80

自引率

6.90%

发文量

1217

审稿时长

2-4 weeks

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.