The incidence and mortality rates of lung cancer have remained high for several decades, necessitating the discovery of new drugs and the development of effective treatment strategies. This study identified matairesinoside (MTS) as a potent inhibitor of TMEM16A, a novel drug target for lung cancer. Molecular simulation combined with site-directed mutagenesis experiments confirmed the key binding sites of MTS and TMEM16A. Cell experiments demonstrated that MTS significantly inhibited the growth, migration, and invasion of lung cancer cells, while inducing apoptosis. Gene knockdown and overexpression studies further revealed that TMEM16A is the target for MTS in regulating lung cancer cell growth. Western blot analysis elucidated the signaling transduction network involved in MTS-mediated regulation of lung cancer. Building upon these findings, a biodegradable self-healing functional hydrogel was developed to load MTS, aiming to enhance therapeutic efficacy and minimize side effects . Animal experiments demonstrated that the hydrogel/MTS formulation exhibited satisfactory inhibitory effects on lung cancer and mitigated the side effects associated with direct MTS injection. This study identified MTS as a potential candidate for anti-lung cancer therapy with well-defined pharmacological mechanisms. Moreover, the targeted drug delivery system utilizing the hydrogel/MTS platform offers a promising approach for lung cancer treatment.

中文翻译：

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Matairesinoside，一种新型TMEM16A离子通道抑制剂，负载功能性水凝胶用于肺癌治疗


几十年来，肺癌的发病率和死亡率一直居高不下，因此需要发现新药并制定有效的治疗策略。这项研究确定 Matairesinoside (MTS) 是 TMEM16A 的有效抑制剂，TMEM16A 是肺癌的新型药物靶点。分子模拟结合定点突变实验证实了MTS和TMEM16A的关键结合位点。细胞实验表明，MTS显着抑制肺癌细胞的生长、迁移和侵袭，同时诱导细胞凋亡。基因敲低和过表达研究进一步表明TMEM16A是MTS调节肺癌细胞生长的靶点。蛋白质印迹分析阐明了参与 MTS 介导的肺癌调节的信号转导网络。基于这些发现，开发了一种可生物降解的自愈功能水凝胶来负载 MTS，旨在提高治疗效果并最大限度地减少副作用。动物实验表明，水凝胶/MTS制剂对肺癌表现出令人满意的抑制作用，并减轻了直接注射MTS相关的副作用。这项研究将 MTS 确定为具有明确药理机制的抗肺癌治疗的潜在候选者。此外，利用水凝胶/MTS平台的靶向药物递送系统为肺癌治疗提供了一种有前景的方法。