化疗药物由于其细胞毒性而可以抑制恶性细胞的增殖，但这种增殖受到附带损伤的限制。二氢青蒿素（DHA）具有选择性抗癌作用，其作用靶点和机制仍不清楚。本工作旨在研究 DHA 的选择性抑制作用及其机制。研究结果显示，与16HBE细胞系（16HBE）相比，Lewis细胞系（LLC）和A549细胞系（A549）具有极快的增殖速度。与 16HBE 相比，LLC 和 A549 显示 NRAS 表达增加。有趣的是，DHA被发现可以抑制LLC和A549的增殖并促进其凋亡，具有显着的抗癌功效和下调NRAS。分子对接和细胞热位移测定的结果表明，DHA 可以与表皮生长因子受体 (EGFR) 分子结合，减弱 EGF 结合，从而驱动抑制作用。 LLC 和 A549 在 DHA 反应下也表现出明显的 DNA 损伤。进一步的结果表明，NRAS 的过度表达减轻了 DHA 诱导的 NRAS 阻断。而且，当NRAS过度表达时，不仅DNA损伤受损，肺癌细胞的增殖也恢复活力。综上所述，DHA可以通过与EGFR结合，从而废除NRAS信号通路，从而导致DNA损伤，从而诱导选择性抗肺癌功效，这为恶性肿瘤的植物药物分子治疗提供了新的理论基础。© 2024。作者( s）。

Chemotherapeutic agents can inhibit the proliferation of malignant cells due to their cytotoxicity, which is limited by collateral damage. Dihydroartemisinin (DHA), has a selective anti-cancer effect, whose target and mechanism remain uncovered. The present work aims to examine the selective inhibitory effect of DHA as well as the mechanisms involved. The findings revealed that the Lewis cell line (LLC) and A549 cell line (A549) had an extremely rapid proliferation rate compared with the 16HBE cell line (16HBE). LLC and A549 showed an increased expression of NRAS compared with 16HBE. Interestingly, DHA was found to inhibit the proliferation and facilitate the apoptosis of LLC and A549 with significant anti-cancer efficacy and down-regulation of NRAS. Results from molecular docking and cellular thermal shift assay revealed that DHA could bind to epidermal growth factor receptor (EGFR) molecules, attenuating the EGF binding and thus driving the suppressive effect. LLC and A549 also exhibited obvious DNA damage in response to DHA. Further results demonstrated that over-expression of NRAS abated DHA-induced blockage of NRAS. Moreover, not only the DNA damage was impaired, but the proliferation of lung cancer cells was also revitalized while NRAS was over-expression. Taken together, DHA could induce selective anti-lung cancer efficacy through binding to EGFR and thereby abolishing the NRAS signaling pathway, thus leading to DNA damage, which provides a novel theoretical basis for phytomedicine molecular therapy of malignant tumors.© 2024. The Author(s).