Hu Shu-Yu, Lin Tsai-Hui, Chen Chung-Yu, He Yu-Hao, Huang Wei-Chien, Hsieh Ching-Yun, Chen Ya-Huey, Chang Wei-Chao
Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404333, Taiwan.
Department of Chinese Medicine, China Medical University Hospital, Taichung 404327, Taiwan.
Pharmaceuticals (Basel). 2024 Oct 11;17(10):1356. doi: 10.3390/ph17101356.
Adjuvant chemotherapy, particularly cisplatin, is recommended for non-small cell lung carcinoma (NSCLC) patients at high risk of recurrence. EF-hand domain-containing protein D2 (EFHD2) has been recently shown to increase cisplatin resistance and is significantly associated with recurrence in early-stage NSCLC patients. Natural products, commonly used as phytonutrients, are also recognized for their potential as pharmaceutical anticancer agents.
In this study, a range of Chinese herbs known for their antitumor or chemotherapy-enhancing properties were evaluated for their ability to inhibit EFHD2 expression in NSCLC cells. Among the herbs tested, () exhibited the highest efficacy in inhibiting EFHD2 and sensitizing cells to cisplatin. Through LC-MS identification and functional assays, coclaurine was identified as a key molecule in responsible for EFHD2 inhibition. Coclaurine not only downregulated EFHD2-related NOX4-ABCC1 signaling and enhanced cisplatin sensitivity, but also suppressed the stemness and metastatic properties of NSCLC cells. Mechanistically, coclaurine disrupted the interaction between the transcription factor FOXG1 and the EFHD2 promoter, leading to a reduction in EFHD2 transcription. Silencing FOXG1 further inhibited EFHD2 expression and sensitized NSCLC cells to cisplatin.
and its active compound coclaurine may serve as effective adjuvant therapies to improve cisplatin efficacy in the treatment of NSCLC.
辅助化疗，尤其是顺铂，推荐用于有高复发风险的非小细胞肺癌（NSCLC）患者。含EF手结构域蛋白D2（EFHD2）最近已被证明可增加顺铂耐药性，并且与早期NSCLC患者的复发显著相关。天然产物，通常用作植物营养素，也因其作为药物抗癌剂的潜力而受到认可。
在本研究中，评估了一系列以其抗肿瘤或增强化疗特性而闻名的中草药抑制NSCLC细胞中EFHD2表达的能力。在所测试的草药中，（）在抑制EFHD2和使细胞对顺铂敏感方面表现出最高的功效。通过液相色谱 - 质谱鉴定和功能测定，可待因被鉴定为（）中负责抑制EFHD2的关键分子。可待因不仅下调了与EFHD2相关的NOX4 - ABCC1信号传导并增强了顺铂敏感性，还抑制了NSCLC细胞的干性和转移特性。从机制上讲，可待因破坏了转录因子FOXG1与EFHD2启动子之间的相互作用，导致EFHD2转录减少。沉默FOXG1进一步抑制EFHD2表达并使NSCLC细胞对顺铂敏感。
（）及其活性化合物可待因可能作为有效的辅助疗法来提高顺铂在NSCLC治疗中的疗效。
