肺癌是全球最常见和致命的癌症，然而目前尚无充分且新颖的药物用于控制该疾病。先前的报道已经提出蛋白激酶通过调节自噬的方式可能对肺癌具有靶向作用。本研究确定了一种三萜皂苷类化合物——马栗皂苷在靶向负责肺癌增殖和迁移的蛋白激酶中的作用。实验数据显示，马栗皂苷明显抑制了肺癌细胞的增殖，通过下调如AKT、mTOR、MEK和ERK等多种蛋白激酶的表达实现。AKT-mTOR 的下调可能会在马栗皂苷存在的情况下，引发一系列促进细胞毒性自噬介导的凋亡事件。此外，马栗皂苷通过下调HIF-1α和VEGF基因的表达，降低了肺癌的迁移和侵袭能力。此外，它还能成功监测EGFR基因的表达，改善肺部组织学，并调节一个DEN诱导的肺癌模型中的生化参数。马栗皂苷在体外毒性预测和红细胞脆弱性实验中均表现为安全和无毒。因此，本研究阐明了马栗皂苷靶向蛋白激酶的分子机制，并暗示其可能成为治疗肺癌更安全和更可行的治疗药物。版权©2023由Elsevier B.V.出版。

Lung cancer is the most common and lethal cancer worldwide, yet there are no adequate and novel medications to control this illness. Previous reports suggested the potential of protein kinases to target lung cancer by regulating autophagy. This study establishes the role of aescin, a triterpenoid saponin, in targeting protein kinases responsible for lung cancer proliferation and mobility. The experimental data revealed that aescin significantly impedes lung cancer cell proliferation by downregulating protein kinases such as AKT, mTOR, MEK, and ERK. Downregulation of AKT-mTOR may promote a string of events inducing cytotoxic autophagy-mediated apoptosis in the presence of aescin. Besides, aescin decreases mobility and invasion by downregulating HIF-1α and VEGF gene expressions. Moreover, it successfully monitors EGFR gene expression, improves lung histology, and regulates biochemical parameters in a pre-clinical DEN-induced lung cancer model. Aescin was observed to be safe and non-toxic in both in silico toxicity predictions and ex vivo erythrocyte fragility assays. Hence, this study elucidates the molecular mechanism of aescin in targeting protein kinases and suggests that it could be a safer and more viable therapeutic agent for lung cancer treatment.Copyright © 2023. Published by Elsevier B.V.