{"title":"二甲双胍通过KLF4调节口腔鳞状细胞癌的干性来克服化疗耐药性","authors":"Tong Zhou, Xuefeng Zhang, Dan Yang, Weideng Wei, Jianguo Gan, Xiaoqiang Xia, Qianming Chen, Jian Jiang, Xiaodong Feng","doi":"10.1111/odi.15075","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Chemoresistance is a common event after chemotherapy, including oral squamous cell carcinoma (OSCC). Accumulated evidence suggests that the cancer stemness significantly contributes to therapy resistance. An unresolved question remains regarding how to effectively overcome OSCC chemoresistance by targeting stemness. This study aims to investigate the antitumor effect of metformin and clarify the potential molecular mechanisms.</p><p><strong>Methods: </strong>Cellular models resistant to chemotherapy were established, and their viability and sphere-forming ability were assessed using CCK-8 and soft agar formation assays, respectively. RNA-seq and Western blotting analyses were employed to delve into the molecular pathways. Furthermore, to corroborate the inhibitory effects of metformin and cisplatin at an animal level, a subcutaneous tumor transplantation model was instituted.</p><p><strong>Results: </strong>Metformin as a monotherapy exhibited inhibition of stemness traits via Krüppel-like factor 4 (KLF4). Metformin and cisplatin can synergically inhibit cell proliferation and induce cell apoptosis. Animal experiments confirmed the inhibitory effect of cisplatin and metformin on tumor in mice.</p><p><strong>Conclusion: </strong>Our study proposes a potential therapeutic approach of combining chemotherapy with metformin to overcome chemoresistance in OSCC.</p>","PeriodicalId":19615,"journal":{"name":"Oral diseases","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Metformin overcomes chemoresistance by regulating stemness via KLF4 in oral squamous cell carcinoma.\",\"authors\":\"Tong Zhou, Xuefeng Zhang, Dan Yang, Weideng Wei, Jianguo Gan, Xiaoqiang Xia, Qianming Chen, Jian Jiang, Xiaodong Feng\",\"doi\":\"10.1111/odi.15075\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Chemoresistance is a common event after chemotherapy, including oral squamous cell carcinoma (OSCC). Accumulated evidence suggests that the cancer stemness significantly contributes to therapy resistance. An unresolved question remains regarding how to effectively overcome OSCC chemoresistance by targeting stemness. This study aims to investigate the antitumor effect of metformin and clarify the potential molecular mechanisms.</p><p><strong>Methods: </strong>Cellular models resistant to chemotherapy were established, and their viability and sphere-forming ability were assessed using CCK-8 and soft agar formation assays, respectively. RNA-seq and Western blotting analyses were employed to delve into the molecular pathways. Furthermore, to corroborate the inhibitory effects of metformin and cisplatin at an animal level, a subcutaneous tumor transplantation model was instituted.</p><p><strong>Results: </strong>Metformin as a monotherapy exhibited inhibition of stemness traits via Krüppel-like factor 4 (KLF4). Metformin and cisplatin can synergically inhibit cell proliferation and induce cell apoptosis. Animal experiments confirmed the inhibitory effect of cisplatin and metformin on tumor in mice.</p><p><strong>Conclusion: </strong>Our study proposes a potential therapeutic approach of combining chemotherapy with metformin to overcome chemoresistance in OSCC.</p>\",\"PeriodicalId\":19615,\"journal\":{\"name\":\"Oral diseases\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-07-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Oral diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/odi.15075\",\"RegionNum\":3,\"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 diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/odi.15075","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
引用次数: 0
摘要
目的:化疗耐药是化疗后的常见现象,包括口腔鳞状细胞癌(OSCC)。积累的证据表明,癌症干性是导致耐药性的重要原因。如何通过靶向干性有效克服OSCC化疗耐药性仍是一个悬而未决的问题。本研究旨在探讨二甲双胍的抗肿瘤作用,并阐明其潜在的分子机制:方法:建立化疗耐药细胞模型,分别用CCK-8和软琼脂形成试验评估其存活率和成球能力。采用 RNA-seq 和 Western 印迹分析深入研究分子通路。此外,为了在动物水平上证实二甲双胍和顺铂的抑制作用,还建立了皮下肿瘤移植模型:结果:二甲双胍作为单一疗法可通过克鲁珀尔样因子4(KLF4)抑制干性特征。二甲双胍和顺铂可协同抑制细胞增殖并诱导细胞凋亡。动物实验证实了顺铂和二甲双胍对小鼠肿瘤的抑制作用:我们的研究提出了一种潜在的治疗方法,即化疗与二甲双胍联合使用,以克服 OSCC 的化疗耐药性。
Metformin overcomes chemoresistance by regulating stemness via KLF4 in oral squamous cell carcinoma.
Objective: Chemoresistance is a common event after chemotherapy, including oral squamous cell carcinoma (OSCC). Accumulated evidence suggests that the cancer stemness significantly contributes to therapy resistance. An unresolved question remains regarding how to effectively overcome OSCC chemoresistance by targeting stemness. This study aims to investigate the antitumor effect of metformin and clarify the potential molecular mechanisms.
Methods: Cellular models resistant to chemotherapy were established, and their viability and sphere-forming ability were assessed using CCK-8 and soft agar formation assays, respectively. RNA-seq and Western blotting analyses were employed to delve into the molecular pathways. Furthermore, to corroborate the inhibitory effects of metformin and cisplatin at an animal level, a subcutaneous tumor transplantation model was instituted.
Results: Metformin as a monotherapy exhibited inhibition of stemness traits via Krüppel-like factor 4 (KLF4). Metformin and cisplatin can synergically inhibit cell proliferation and induce cell apoptosis. Animal experiments confirmed the inhibitory effect of cisplatin and metformin on tumor in mice.
Conclusion: Our study proposes a potential therapeutic approach of combining chemotherapy with metformin to overcome chemoresistance in OSCC.
期刊介绍:
Oral Diseases is a multidisciplinary and international journal with a focus on head and neck disorders, edited by leaders in the field, Professor Giovanni Lodi (Editor-in-Chief, Milan, Italy), Professor Stefano Petti (Deputy Editor, Rome, Italy) and Associate Professor Gulshan Sunavala-Dossabhoy (Deputy Editor, Shreveport, LA, USA). The journal is pre-eminent in oral medicine. Oral Diseases specifically strives to link often-isolated areas of dentistry and medicine through broad-based scholarship that includes well-designed and controlled clinical research, analytical epidemiology, and the translation of basic science in pre-clinical studies. The journal typically publishes articles relevant to many related medical specialties including especially dermatology, gastroenterology, hematology, immunology, infectious diseases, neuropsychiatry, oncology and otolaryngology. The essential requirement is that all submitted research is hypothesis-driven, with significant positive and negative results both welcomed. Equal publication emphasis is placed on etiology, pathogenesis, diagnosis, prevention and treatment.