Abstract：
The advanced non-small cell lung cancer (NSCLC) that harbors epidermal growth factor receptor (EGFR) mutations has put a selective pressure on the discovery and development of newer EGFR inhibitors. Therefore, the present study intends to explore the pharmacological effect of Araguspongine C (Aragus-C) as anticancer agent against lung cancer. The effect of Aragus-C was evaluated on the viability of the A549 and H1975 cells. Further biochemical assays were performed to elaborate the effect of Aragus-C, on the apoptosis, cell-cycle analysis, and mitochondrial membrane potential in A549 cells. Western blot analysis was also conducted to determine the expression of EGFR in A549 cells. Tumor xenograft mice model from A549 cells was established to further elaborate the pharmacological activity of Aragus-C. Results suggest that Aragus C showed significant inhibitory activity against A549 cells as compared to H1975 cells. It has been found that Aragus-C causes the induction of apoptosis and promotes cell-cycle arrest at the G2/M phase of A549 cells. It also showed a reduction in the overexpression of EGFR in A549 cells. In tumor xenograft mice model, it showed a significant reduction of tumor volume in a dose-dependent manner, with maximum inhibitory activity was reported by the 8 mg/kg treated group. It also showed significant anti-inflammatory and antioxidant activity by reducing the level of TNF-α, IL-1β, IL-6, and MDA, with a simultaneous increase of superoxide dismutase and glutathione peroxidase. We have demonstrated the potent anti-lung cancer activity of Aragus-C, and it may be considered as a potential therapeutic choice for NSCLC treatment.
摘要：
具有表皮生长因子受体（EGFR）突变的晚期非小细胞肺癌（NSCLC）给新型EGFR抑制剂的发现和开发带来了选择性压力。因此,本研究旨在探讨AraguspongineC（Aragus-C）作为抗癌药物对肺癌的药理作用。评价Aragus-C对A549和H1975细胞的活力的影响。进行了进一步的生化测定以阐述Aragus-C的作用，关于细胞凋亡，细胞周期分析，A549细胞的线粒体膜电位。还进行蛋白质印迹分析以确定EGFR在A549细胞中的表达。建立A549细胞移植瘤小鼠模型，以进一步阐述Aragus-C的药理活性。结果表明，与H1975细胞相比，AragusC对A549细胞显示出明显的抑制活性。已发现Aragus-C引起凋亡的诱导并促进A549细胞在G2/M期的细胞周期停滞。它还显示A549细胞中EGFR的过表达减少。在肿瘤异种移植小鼠模型中，它以剂量依赖的方式显示肿瘤体积显著减小，8mg/kg治疗组报告了最大抑制活性。它还显示了显着的抗炎和抗氧化活性，通过降低TNF-α的水平，IL-1β,IL-6和MDA,同时增加超氧化物歧化酶和谷胱甘肽过氧化物酶。我们已经证明了Aragus-C的有效抗肺癌活性，它可能被认为是NSCLC治疗的潜在治疗选择。
