Gan Wen, Chen Chong, Huang Miaolong, Li Youtao
Department of Thoracic Surgery, Yuebei People Hospital Affiliated to Medical College of Shantou University, Shaoguan, Guangdong 512000, P.R. China.
Oncol Lett. 2024 Sep 24;28(6):560. doi: 10.3892/ol.2024.14693. eCollection 2024 Dec.
The present study aimed to investigate the molecular mechanisms by which paeonol impedes DNA damage repair, induces apoptosis and inhibits cell viability via the mitogen-activated protein kinase (MAPK) pathway. Firstly, normal human bronchial epithelial cells (BEAS-2B) and non-small cell lung cancer cells (H1299) were employed in the study as cellular models. Following cultivation, the cells were divided into experimental and control groups, and were treated with different concentrations of paeonol. Subsequently, various techniques, including western blotting, Cell Counting Kit-8, colony formation, TUNEL and comet assays were conducted to evaluate the effects of paeonol on cell viability, colony-forming ability, apoptosis levels and DNA damage in H1299 cells. According to the experimental results, paeonol significantly reduced the viability and colony formation ability of H1299 cells, but substantially increased apoptosis and DNA damage. These effects were enhanced in response to higher concentrations of paeonol. Furthermore, western blot analysis revealed that paeonol treatment decreased the protein levels of B-cell lymphoma 2 and breast cancer susceptibility gene 1, while it increased the expression levels of cleaved-PARP, cleaved-caspase 3, γH2AX and P21. Additionally, the phosphorylated levels of extracellular signal-regulated kinase 1, c-Jun N-terminal kinase and P38 within the MAPK signaling pathway were diminished. Collectively, the present study demonstrated that paeonol may inhibit the metabolic activity and proliferative capability of H1299 cells, and that it could promote apoptosis and obstruct DNA damage repair by modulating the MAPK signaling pathway.
本研究旨在探讨丹皮酚通过丝裂原活化蛋白激酶（MAPK）途径阻碍DNA损伤修复、诱导细胞凋亡并抑制细胞活力的分子机制。首先，本研究采用正常人支气管上皮细胞（BEAS-2B）和非小细胞肺癌细胞（H1299）作为细胞模型。培养后，将细胞分为实验组和对照组，并用不同浓度的丹皮酚进行处理。随后，进行了包括蛋白质印迹法、细胞计数试剂盒-8、集落形成、TUNEL和彗星试验等各种技术，以评估丹皮酚对H1299细胞活力、集落形成能力、凋亡水平和DNA损伤的影响。根据实验结果，丹皮酚显著降低了H1299细胞的活力和集落形成能力，但大幅增加了细胞凋亡和DNA损伤。随着丹皮酚浓度的升高，这些作用增强。此外，蛋白质印迹分析显示，丹皮酚处理降低了B细胞淋巴瘤2和乳腺癌易感基因1的蛋白质水平，同时增加了裂解的PARP、裂解的半胱天冬酶3、γH2AX和P21的表达水平。此外，MAPK信号通路中细胞外信号调节激酶1、c-Jun氨基末端激酶和P38的磷酸化水平降低。总体而言，本研究表明，丹皮酚可能抑制H1299细胞的代谢活性和增殖能力，并通过调节MAPK信号通路促进细胞凋亡和阻碍DNA损伤修复。
