Although some important advances have been achieved in clinical and diagnosis in the past few years, the management of non-small cell lung cancer (NSCLC) is ultimately dissatisfactory due to the low overall cure and survival rates. Epidermal growth factor (EGFR) has been recognized as a carcinogenic driver and is a crucial pharmacological target for NSCLC. DMU-212, an analog of resveratrol, has been reported to have significant inhibitory effects on several types of cancer. However, the effect of DMU-212 on lung cancer remains unclear. Therefore, this study aims to determine the effects and underlying mechanism of DMU-212 on EGFR-mutant NSCLC cells. The data found that the cytotoxicity of DMU-212 on three EGFR-mutant NSCLC cell lines was significantly higher than that of normal lung epithelial cell. Further study showed that DMU-212 can regulate the expression of cell cycle-related proteins including p21 and cyclinB1 to induce G2/M phase arrest in both H1975 and PC9. Moreover, treatment with DMU-212 significantly promoted the activation of AMPK and simultaneously down-regulated the expression of EGFR and the phosphorylation of PI3K, Akt and ERK. In conclusion, our study suggested that DMU-212 inhibited the growth of NSCLCs via targeting of AMPK and EGFR.

尽管过去几年在临床和诊断方面取得了一些重要进展，但由于总体治愈率和生存率较低，非小细胞肺癌（NSCLC）的治疗最终并不令人满意。表皮生长因子 (EGFR) 已被公认为致癌驱动因素，并且是 NSCLC 的重要药理学靶点。据报道，DMU-212 是白藜芦醇的类似物，对多种癌症具有显着的抑制作用。然而，DMU-212 对肺癌的影响仍不清楚。因此，本研究旨在确定 DMU-212 对 EGFR 突变 NSCLC 细胞的影响和潜在机制。数据发现DMU-212对三种EGFR突变NSCLC细胞系的细胞毒性明显高于正常肺上皮细胞。进一步的研究表明，DMU-212 可以调节细胞周期相关蛋白的表达，包括 p21 和 cyclinB1，从而在 H1975 和 PC9 中诱导 G2/M 期停滞。此外，用 DMU-212 处理可显着促进 AMPK 的激活，同时下调 EGFR 的表达和 PI3K、Akt 和 ERK 的磷酸化。总之，我们的研究表明 DMU-212 通过靶向 AMPK 和 EGFR 抑制 NSCLC 的生长。