非小细胞肺癌是全球面临的一个具有挑战性的疾病。本研究旨在确定将表皮生长因子受体（EGFR）抑制剂埃洛替尼与间质-上皮转化因子（c-Met）抑制剂卡波替尼联合使用，是否对A549细胞具有较强的治疗效果。通过MTT测定，与每种单药≥10 µM的情况相比，埃洛替尼和卡波替尼（5 µM）的联合治疗抑制了A549细胞的存活能力。使用划痕愈合实验，联合治疗相对于单药治疗也更有效地抑制了细胞迁移。此外，通过mRNA表达分析来评估凋亡、转移和细胞周期相关基因，结果显示联合治疗明显抑制了BCL-2、MMP-9、VEGF和TGF-β的表达水平，同时诱导了p53、p21和BAX的表达。在肿瘤标志物方面，免疫印迹分析显示，联合治疗明显降低了BCl-2的表达，并提高了caspase3、p53和p21蛋白的表达，作为凋亡途径的细胞死亡指标。联合治疗对肿瘤体内的抗肿瘤效果显示出明显的肿瘤抑制能力，相较于单药治疗。综上所述，联合治疗可能是治疗非小细胞肺癌的一种潜在的有希望的策略。© 2023 The Author(s).

Non-small cell lung carcinoma is a challenging disease worldwide. This study aims to determine whether combining erlotinib, an epidermal growth factor receptor (EGFR) inhibitor, with cabozantinib, a mesenchymal-epithelial transition factor (c-Met) inhibitor, would have an augmented therapeutic benefit on A549 cells. The combination of erlotinib and cabozantinib (5 µM) inhibited A549 cell viability compared to each monotherapy at ≥ 10 µM as confirmed by the MTT assay. Combination therapy also has a more potent inhibition of cellular migration than monotherapy using the wound-healing assay. Furthermore, mRNA expression analyses for assessing apoptosis, metastasis, and cell cycle-related genes, the results showed that combination therapy significantly inhibits levels of BCL-2, MMP-9, VEGF, and TGF-β while inducing p53, p21, and BAX expression. In terms of oncogenic markers, western blotting analysis showed a significant reduction of BCl-2 expression and elevation in caspase3, p53, and p21 proteins as indicators of cell death via apoptosis. The antitumor in vivo effect of the combination therapy showed significant tumor inhibition compared to monotherapy. In conclusion, combination therapy could be a potential promising strategy to treat non-small cell lung carcinoma.© 2023 The Author(s).