Maria Eduarda Pérez-de-Oliveira , Vivian Petersen Wagner , Colin D. Bingle , Pablo Agustin Vargas , Lynne Bingle
{"title":"粘液表皮样癌致癌途径的中断:CREB 抑制剂 666.15 作为一种潜在的治疗药物","authors":"Maria Eduarda Pérez-de-Oliveira , Vivian Petersen Wagner , Colin D. Bingle , Pablo Agustin Vargas , Lynne Bingle","doi":"10.1016/j.oraloncology.2024.107029","DOIUrl":null,"url":null,"abstract":"<div><div><strong>Objectives:</strong> Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumour with around 50 % of cases carrying the CRTC1-MAML2 translocation. The CREB pathway has been associated with the transforming activity of this translocation. The aim of this study was to determine the effects of CREB inhibition on MEC cell behaviour <em>in vitro</em>. <strong>Material and Methods:</strong> Two translocation-positive (UM-HMC-2 and H292) and one translocation-negative (H253) MEC cell lines were treated with 666.15, a CREB inhibitor. Drug IC50 doses were determined for each cell line. Clonogenic and spheroid assays were used to assess survival, including percentage of cancer stem cells, and transwell and scratch assays evaluated invasive and migratory capacities, respectively. Immunofluorescence staining was used to determine E-cadherin expression. <strong>Results:</strong> CREB inhibition significantly reduced the number of surviving colonies and spheroids and delayed cell invasion in all cell lines, but this was more significant in the fusion positive, UM-HMC-2 cells. The expression of E-cadherin was significantly higher in treated UM-HMC-2 and H292 cells. <strong>Conclusion:</strong> CREB inhibition with 666.15 impaired key MEC oncogenic behaviours associated with metastasis and drug resistance, including cell invasion and survival.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"159 ","pages":"Article 107029"},"PeriodicalIF":4.0000,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Disruption of oncogenic pathways in mucoepidermoid carcinoma: CREB inhibitor 666.15 as a potential therapeutic agent\",\"authors\":\"Maria Eduarda Pérez-de-Oliveira , Vivian Petersen Wagner , Colin D. Bingle , Pablo Agustin Vargas , Lynne Bingle\",\"doi\":\"10.1016/j.oraloncology.2024.107029\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div><strong>Objectives:</strong> Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumour with around 50 % of cases carrying the CRTC1-MAML2 translocation. The CREB pathway has been associated with the transforming activity of this translocation. The aim of this study was to determine the effects of CREB inhibition on MEC cell behaviour <em>in vitro</em>. <strong>Material and Methods:</strong> Two translocation-positive (UM-HMC-2 and H292) and one translocation-negative (H253) MEC cell lines were treated with 666.15, a CREB inhibitor. Drug IC50 doses were determined for each cell line. Clonogenic and spheroid assays were used to assess survival, including percentage of cancer stem cells, and transwell and scratch assays evaluated invasive and migratory capacities, respectively. Immunofluorescence staining was used to determine E-cadherin expression. <strong>Results:</strong> CREB inhibition significantly reduced the number of surviving colonies and spheroids and delayed cell invasion in all cell lines, but this was more significant in the fusion positive, UM-HMC-2 cells. The expression of E-cadherin was significantly higher in treated UM-HMC-2 and H292 cells. <strong>Conclusion:</strong> CREB inhibition with 666.15 impaired key MEC oncogenic behaviours associated with metastasis and drug resistance, including cell invasion and survival.</div></div>\",\"PeriodicalId\":19716,\"journal\":{\"name\":\"Oral oncology\",\"volume\":\"159 \",\"pages\":\"Article 107029\"},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2024-09-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Oral oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1368837524003476\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DENTISTRY, ORAL SURGERY & MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oral oncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1368837524003476","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
Disruption of oncogenic pathways in mucoepidermoid carcinoma: CREB inhibitor 666.15 as a potential therapeutic agent
Objectives: Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumour with around 50 % of cases carrying the CRTC1-MAML2 translocation. The CREB pathway has been associated with the transforming activity of this translocation. The aim of this study was to determine the effects of CREB inhibition on MEC cell behaviour in vitro. Material and Methods: Two translocation-positive (UM-HMC-2 and H292) and one translocation-negative (H253) MEC cell lines were treated with 666.15, a CREB inhibitor. Drug IC50 doses were determined for each cell line. Clonogenic and spheroid assays were used to assess survival, including percentage of cancer stem cells, and transwell and scratch assays evaluated invasive and migratory capacities, respectively. Immunofluorescence staining was used to determine E-cadherin expression. Results: CREB inhibition significantly reduced the number of surviving colonies and spheroids and delayed cell invasion in all cell lines, but this was more significant in the fusion positive, UM-HMC-2 cells. The expression of E-cadherin was significantly higher in treated UM-HMC-2 and H292 cells. Conclusion: CREB inhibition with 666.15 impaired key MEC oncogenic behaviours associated with metastasis and drug resistance, including cell invasion and survival.
期刊介绍:
Oral Oncology is an international interdisciplinary journal which publishes high quality original research, clinical trials and review articles, editorials, and commentaries relating to the etiopathogenesis, epidemiology, prevention, clinical features, diagnosis, treatment and management of patients with neoplasms in the head and neck.
Oral Oncology is of interest to head and neck surgeons, radiation and medical oncologists, maxillo-facial surgeons, oto-rhino-laryngologists, plastic surgeons, pathologists, scientists, oral medical specialists, special care dentists, dental care professionals, general dental practitioners, public health physicians, palliative care physicians, nurses, radiologists, radiographers, dieticians, occupational therapists, speech and language therapists, nutritionists, clinical and health psychologists and counselors, professionals in end of life care, as well as others interested in these fields.