Department of Radiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
Department of Pathology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, Hunan, China.
J Biochem Mol Toxicol. 2023 Jun;37(6):e23328. doi: 10.1002/jbt.23328. Epub 2023 Feb 19.
Deregulation of epidermal growth factor receptor (EGFR) signaling is frequently observed in non-small cell lung cancer (NSCLC). The present study aimed to determine the impact of dihydromyricetin (DHM) on NSCLC, a natural compound extracted from Ampelopsis grossedentata with various pharmacological activities. Results of the present study demonstrated that DHM may act as a promising antitumor agent for NSCLC therapy, inhibiting the growth of cancer cells in vitro and in vivo. Mechanistically, results of the present study demonstrated that exposure to DHM downregulated the activity of wild-type (WT) and mutant EGFRs (mutations, exon 19 deletion, and L858R/T790M mutation). Moreover, western blot analysis indicated that DHM induced cell apoptosis via suppression of the antiapoptotic protein, survivin. Results of the present study further demonstrated that depletion or activation of EGFR/Akt signaling may regulate survivin expression though modulating ubiquitination. Collectively, these results suggested that DHM may act as a potential EGFR inhibitor, and may provide a novel choice of treatment strategy for patients with NSCLC.
表皮生长因子受体 (EGFR) 信号的失调在非小细胞肺癌 (NSCLC) 中经常观察到。本研究旨在确定二氢杨梅素 (DHM) 对 NSCLC 的影响，DHM 是从显齿蛇葡萄中提取的具有多种药理活性的天然化合物。本研究结果表明，DHM 可能作为一种有前途的 NSCLC 治疗抗肿瘤药物，在体外和体内抑制癌细胞的生长。从机制上讲，本研究结果表明，暴露于 DHM 下调了野生型 (WT) 和突变型 EGFR (突变，外显子 19 缺失和 L858R/T790M 突变) 的活性。此外，Western blot 分析表明，DHM 通过抑制抗凋亡蛋白生存素诱导细胞凋亡。本研究进一步表明，通过调节泛素化，EGFR/Akt 信号的耗竭或激活可能调节生存素的表达。总之，这些结果表明，DHM 可能作为一种潜在的 EGFR 抑制剂，为 NSCLC 患者提供一种新的治疗策略选择。
