Saracatinib is an oral Src‐kinase inhibitor and has been studied in preclinical models and clinical trials of cancer therapy. GMI, a fungal immunomodulatory protein from Ganoderma microsporum, possesses antitumor capacity. The aim of this study is to evaluate the cytotoxic effect of combination treatment with saracatinib and GMI on parental and pemetrexed‐resistant lung cancer cells. Cotreatment with saracatinib and GMI induced synergistic and additive cytotoxic effect in A549 and A400 cells by annexin V/propidium iodide assay and combination index. Using western blot assay, saracatinib, and GMI combined treatment synergistically induced caspase‐7 activation in A549 cells. Different from A549 cells, saracatinib and GMI cotreatment markedly increased LC3B‐II in A400 cells. ATG5 silencing abolished the caspase‐7 activation and reduced cell death in A549 cells after cotreatment. This is the first study to provide a novel strategy of treating lung cancer with or without drug resistance via combination treatment with GMI and saracatinib.

中文翻译：

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Src 抑制剂 Saracatinib 与 GMI（一种灵芝小孢子菌免疫调节蛋白）的联合治疗通过肺癌细胞的自噬和凋亡诱导合成致死。

Saracatinib 是一种口服 Src 激酶抑制剂，已在癌症治疗的临床前模型和临床试验中进行了研究。GMI，一种来自小孢子灵芝的真菌免疫调节蛋白，具有抗肿瘤能力。本研究的目的是评估萨拉卡替尼和 GMI 联合治疗对父母和培美曲塞耐药肺癌细胞的细胞毒性作用。通过膜联蛋白 V/碘化丙啶测定和组合指数，萨拉卡替尼和 GMI 共同处理在 A549 和 A400 细胞中诱导了协同和累加的细胞毒作用。使用蛋白质印迹分析，saracatinib 和 GMI 联合治疗协同诱导 A549 细胞中的 caspase-7 活化。与 A549 细胞不同，萨拉卡替尼和 GMI 联合处理显着增加了 A400 细胞中的 LC3B-II。ATG5 沉默消除了 Caspase-7 活化并减少了 A549 细胞在共处理后的细胞死亡。这是第一项提供通过与 GMI 和萨拉卡替尼联合治疗治疗有或没有耐药性肺癌的新策略的研究。