{"title":"新型 OCT1 抑制剂 NIO-1 可增强射频消融对肝细胞癌的抗肿瘤作用","authors":"Hua Yang, Yang Yang, Xiaozheng Zou, Qian Zhang, Xiaoli Li, Chunyu Zhang, Yanan Wang, Lili Ren","doi":"10.2174/1566524023666230526154739","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Radiofrequency ablation (RFA) is an important treatment strategy for patients with advanced hepatocellular carcinoma (HCC). However, its therapeutic effect is unsatisfactory and recurrence often occurs after RFA treatment. The octamer-binding transcription factor OCT1 is a novel tumour-promoting factor and an ideal target for HCC therapy.</p><p><strong>Objective: </strong>This study aimed to expand the understanding of HCC regulation by OCT1.</p><p><strong>Methods: </strong>The expression levels of the target genes were examined using qPCR. The inhibitory effects of a novel inhibitor of OCT1 (NIO-1) on HCC cells and OCT1 activation were examined using Chromatin immunoprecipitation or cell survival assays. RFA was performed in a subcutaneous tumour model of nude mice.</p><p><strong>Results: </strong>Patients with high OCT1 expression in the tumour tissue had a poor prognosis after RFA treatment (n = 81). The NIO-1 showed antitumor activity against HCC cells and downregulated the expression of the downstream genes of OCT1 in HCC cells, including those associated with cell proliferation (matrix metalloproteinase-3) and epithelial-mesenchymal transition-related factors (Snail, Twist, N-cadherin, and vimentin). In a subcutaneous murine model of HCC, NIO-1 enhanced the effect of RFA treatment on HCC tissues (n = 8 for NIO-1 and n = 10 for NIO-1 + RFA).</p><p><strong>Conclusion: </strong>This study demonstrated the clinical importance of OCT1 expression in HCC for the first time. Our findings also revealed that NIO-1 aids RFA therapy by targeting OCT1.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.2000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"NIO-1, A Novel Inhibitor of OCT1, Enhances the Antitumor Action of Radiofrequency Ablation against Hepatocellular Carcinoma.\",\"authors\":\"Hua Yang, Yang Yang, Xiaozheng Zou, Qian Zhang, Xiaoli Li, Chunyu Zhang, Yanan Wang, Lili Ren\",\"doi\":\"10.2174/1566524023666230526154739\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Radiofrequency ablation (RFA) is an important treatment strategy for patients with advanced hepatocellular carcinoma (HCC). However, its therapeutic effect is unsatisfactory and recurrence often occurs after RFA treatment. The octamer-binding transcription factor OCT1 is a novel tumour-promoting factor and an ideal target for HCC therapy.</p><p><strong>Objective: </strong>This study aimed to expand the understanding of HCC regulation by OCT1.</p><p><strong>Methods: </strong>The expression levels of the target genes were examined using qPCR. The inhibitory effects of a novel inhibitor of OCT1 (NIO-1) on HCC cells and OCT1 activation were examined using Chromatin immunoprecipitation or cell survival assays. RFA was performed in a subcutaneous tumour model of nude mice.</p><p><strong>Results: </strong>Patients with high OCT1 expression in the tumour tissue had a poor prognosis after RFA treatment (n = 81). The NIO-1 showed antitumor activity against HCC cells and downregulated the expression of the downstream genes of OCT1 in HCC cells, including those associated with cell proliferation (matrix metalloproteinase-3) and epithelial-mesenchymal transition-related factors (Snail, Twist, N-cadherin, and vimentin). In a subcutaneous murine model of HCC, NIO-1 enhanced the effect of RFA treatment on HCC tissues (n = 8 for NIO-1 and n = 10 for NIO-1 + RFA).</p><p><strong>Conclusion: </strong>This study demonstrated the clinical importance of OCT1 expression in HCC for the first time. Our findings also revealed that NIO-1 aids RFA therapy by targeting OCT1.</p>\",\"PeriodicalId\":10873,\"journal\":{\"name\":\"Current molecular medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current molecular medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/1566524023666230526154739\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current molecular medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/1566524023666230526154739","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
NIO-1, A Novel Inhibitor of OCT1, Enhances the Antitumor Action of Radiofrequency Ablation against Hepatocellular Carcinoma.
Background: Radiofrequency ablation (RFA) is an important treatment strategy for patients with advanced hepatocellular carcinoma (HCC). However, its therapeutic effect is unsatisfactory and recurrence often occurs after RFA treatment. The octamer-binding transcription factor OCT1 is a novel tumour-promoting factor and an ideal target for HCC therapy.
Objective: This study aimed to expand the understanding of HCC regulation by OCT1.
Methods: The expression levels of the target genes were examined using qPCR. The inhibitory effects of a novel inhibitor of OCT1 (NIO-1) on HCC cells and OCT1 activation were examined using Chromatin immunoprecipitation or cell survival assays. RFA was performed in a subcutaneous tumour model of nude mice.
Results: Patients with high OCT1 expression in the tumour tissue had a poor prognosis after RFA treatment (n = 81). The NIO-1 showed antitumor activity against HCC cells and downregulated the expression of the downstream genes of OCT1 in HCC cells, including those associated with cell proliferation (matrix metalloproteinase-3) and epithelial-mesenchymal transition-related factors (Snail, Twist, N-cadherin, and vimentin). In a subcutaneous murine model of HCC, NIO-1 enhanced the effect of RFA treatment on HCC tissues (n = 8 for NIO-1 and n = 10 for NIO-1 + RFA).
Conclusion: This study demonstrated the clinical importance of OCT1 expression in HCC for the first time. Our findings also revealed that NIO-1 aids RFA therapy by targeting OCT1.
期刊介绍:
Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews/ mini-reviews, original research articles, short communications/letters and drug clinical trial studies on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal invites guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.