{"title":"苦参酚A靶向抑制IDO1增强非小细胞肺癌的放射敏感性。","authors":"Yingwei Zhu , Yunqian Chu , Hanjue Dai , Enci Lu , Qian Geng , Qingying Xian , Hua Jiang , Wenyu Zhu","doi":"10.1016/j.pupt.2025.102362","DOIUrl":null,"url":null,"abstract":"<div><div>Kushenol, a monomeric compound, was extracted from the roots of the medicinal plant Sophora flavescens. To explore the activity of Kushenol A in non-small cell lung cancer (NSCLC), CCK-8 assay, flow cytometry, and Western blot were performed. A xenograft mouse model was established. Our results demonstrated that Kushenol A treatment significantly enhanced the killing effect of radiation on NSCLC cells. Co-treatment with radiation and Kushenol A markedly reduced cell viability, increased intracellular ROS levels, and elevated the proportion of apoptotic cells compared to NSCLC cells treated with radiation alone. Animal experiments further confirmed that radiation therapy with simultaneous Kushenol A administration suppressed tumor growth and improved radiotherapy sensitivity compared to mice treated with radiation alone. Furthermore, Kushenol A did not produce significant toxic damage to the major organs of mice. Mechanistically, radiation therapy combined with Kushenol A treatment significantly upregulated protein levels of cleaved Caspase-3 and cleaved Caspase-9, leading to Bax translocation from the cytoplasm to mitochondria. Concurrently, Kushenol A treatment reduced NRF2 levels in the cytoplasm, thereby promoting an increase in ROS levels. Notably, Kushenol A enhanced tumor radiosensitivity by targeted inhibition of Indoleamine 2,3-dioxygenase 1 (IDO1). Taken together, our findings suggested that cotreatment with Kushenol A and radiation promoted the entry of Bax into mitochondria and activated the mitochondrial apoptotic pathway. Kushenol A exhibited targeted inhibition of IDO1, enhancing the sensitivity of non-small cell lung cancer to radiotherapy.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"90 ","pages":"Article 102362"},"PeriodicalIF":2.8000,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Targeted inhibition of IDO1 by Kushenol A enhances radiosensitivity in non-small cell lung cancer\",\"authors\":\"Yingwei Zhu , Yunqian Chu , Hanjue Dai , Enci Lu , Qian Geng , Qingying Xian , Hua Jiang , Wenyu Zhu\",\"doi\":\"10.1016/j.pupt.2025.102362\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Kushenol, a monomeric compound, was extracted from the roots of the medicinal plant Sophora flavescens. To explore the activity of Kushenol A in non-small cell lung cancer (NSCLC), CCK-8 assay, flow cytometry, and Western blot were performed. A xenograft mouse model was established. Our results demonstrated that Kushenol A treatment significantly enhanced the killing effect of radiation on NSCLC cells. Co-treatment with radiation and Kushenol A markedly reduced cell viability, increased intracellular ROS levels, and elevated the proportion of apoptotic cells compared to NSCLC cells treated with radiation alone. Animal experiments further confirmed that radiation therapy with simultaneous Kushenol A administration suppressed tumor growth and improved radiotherapy sensitivity compared to mice treated with radiation alone. Furthermore, Kushenol A did not produce significant toxic damage to the major organs of mice. Mechanistically, radiation therapy combined with Kushenol A treatment significantly upregulated protein levels of cleaved Caspase-3 and cleaved Caspase-9, leading to Bax translocation from the cytoplasm to mitochondria. Concurrently, Kushenol A treatment reduced NRF2 levels in the cytoplasm, thereby promoting an increase in ROS levels. Notably, Kushenol A enhanced tumor radiosensitivity by targeted inhibition of Indoleamine 2,3-dioxygenase 1 (IDO1). Taken together, our findings suggested that cotreatment with Kushenol A and radiation promoted the entry of Bax into mitochondria and activated the mitochondrial apoptotic pathway. Kushenol A exhibited targeted inhibition of IDO1, enhancing the sensitivity of non-small cell lung cancer to radiotherapy.</div></div>\",\"PeriodicalId\":20799,\"journal\":{\"name\":\"Pulmonary pharmacology & therapeutics\",\"volume\":\"90 \",\"pages\":\"Article 102362\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-06-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pulmonary pharmacology & therapeutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1094553925000197\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pulmonary pharmacology & therapeutics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1094553925000197","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Targeted inhibition of IDO1 by Kushenol A enhances radiosensitivity in non-small cell lung cancer
Kushenol, a monomeric compound, was extracted from the roots of the medicinal plant Sophora flavescens. To explore the activity of Kushenol A in non-small cell lung cancer (NSCLC), CCK-8 assay, flow cytometry, and Western blot were performed. A xenograft mouse model was established. Our results demonstrated that Kushenol A treatment significantly enhanced the killing effect of radiation on NSCLC cells. Co-treatment with radiation and Kushenol A markedly reduced cell viability, increased intracellular ROS levels, and elevated the proportion of apoptotic cells compared to NSCLC cells treated with radiation alone. Animal experiments further confirmed that radiation therapy with simultaneous Kushenol A administration suppressed tumor growth and improved radiotherapy sensitivity compared to mice treated with radiation alone. Furthermore, Kushenol A did not produce significant toxic damage to the major organs of mice. Mechanistically, radiation therapy combined with Kushenol A treatment significantly upregulated protein levels of cleaved Caspase-3 and cleaved Caspase-9, leading to Bax translocation from the cytoplasm to mitochondria. Concurrently, Kushenol A treatment reduced NRF2 levels in the cytoplasm, thereby promoting an increase in ROS levels. Notably, Kushenol A enhanced tumor radiosensitivity by targeted inhibition of Indoleamine 2,3-dioxygenase 1 (IDO1). Taken together, our findings suggested that cotreatment with Kushenol A and radiation promoted the entry of Bax into mitochondria and activated the mitochondrial apoptotic pathway. Kushenol A exhibited targeted inhibition of IDO1, enhancing the sensitivity of non-small cell lung cancer to radiotherapy.
期刊介绍:
Pulmonary Pharmacology and Therapeutics (formerly Pulmonary Pharmacology) is concerned with lung pharmacology from molecular to clinical aspects. The subject matter encompasses the major diseases of the lung including asthma, cystic fibrosis, pulmonary circulation, ARDS, carcinoma, bronchitis, emphysema and drug delivery. Laboratory and clinical research on man and animals will be considered including studies related to chemotherapy of cancer, tuberculosis and infection. In addition to original research papers the journal will include review articles and book reviews.
Research Areas Include:
• All major diseases of the lung
• Physiology
• Pathology
• Drug delivery
• Metabolism
• Pulmonary Toxicology.