一二三四区视频,亚洲少妇熟女色,日本久热无码视频网,欧美国产日韩大尺度,亚洲a视频,久久少妇一区二区,日韩999无码视频,刺激久久久久久久,啊啊啊啊不要啊在线

ChemicalBook >> journal list >> Cancer Science >>article
Cancer Science

Cancer Science

IF: 4.5
Download PDF

Dauricine Overcomes Osimertinib Resistance in Lung Cancer by Inducing Ferroptosis via Stabilizing SAT1

Published:8 June 2025 DOI: 10.1111/cas.70113 PMID: 40485050
Biying Men, Zhijie Chen, Haotian Ge, Zhuoying Yang, Liang Yun, Jianjun Jiang, Meijuan Dian, Yujing He, Zehao Zhou, Ruihao Zhang, Tianbao Yan, Zichao Li, Yingxin Zhang, Yongjie He, Junming He, Xuguang Rao, Shuan Rao

Abstract

Osimertinib is a third-generation EGFR tyrosine kinase inhibitor (TKI) widely used to treat advanced nonsmall cell lung cancer (NSCLC) with EGFR mutations. However, resistance to osimertinib frequently develops, limiting its long-term effectiveness. In this study, we used osimertinib-resistant lung cancer cell lines and lung cancer patient-derived organoids to demonstrate the potential of dauricine, a bioactive compound derived from menispermum dauricum, to overcome osimertinib resistance in lung cancer cells. Mechanistic studies reveal that dauricine, when combined with osimertinib, efficiently induces ferroptosis in resistant lung cancer cells. Notably, RNA interference and pharmacological inhibition assays identify SAT1, a key enzyme involved in polyamine metabolism and oxidative stress regulation, as a critical mediator of the synergistic effects observed with the dauricine-osimertinib combination therapy. Furthermore, we show that dauricine can directly interact with and stabilize SAT1 to enhance its activity. In?vivo, when administered with osimertinib, dauricine significantly suppresses tumor growth in osimertinib-resistant lung cancer models. These findings provide novel insights into the role of SAT1 in overcoming osimertinib resistance and suggest that combining dauricine with osimertinib could be a promising therapeutic strategy to improve the efficacy of EGFR-TKI therapy in resistant NSCLC.

康定县| 剑阁县| 玉溪市| 临城县| 班戈县| 晋中市| 舟山市| 宣威市| 耿马| 浦东新区| 广汉市| 岗巴县| 阜康市| 渭南市| 尼木县| 韩城市| 富源县| 诸城市| 宁晋县| 额敏县| 措美县| 济宁市| 台前县| 交口县| 博湖县| 枝江市| 勃利县| 陇南市| 玉环县| 清水县| 星子县| 攀枝花市| 绥滨县| 德昌县| 哈尔滨市| 塘沽区| 镇平县| 西吉县| 从化市| 太白县| 夏河县|