Lung Cancer Center, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Nutr Cancer. 2022;74(2):735-746. doi: 10.1080/01635581.2021.1912368. Epub 2021 Apr 16.
Trilobatin is a common type of flavonoids compounds derived from Rehd leaves. Previous report suggests that trilobatin was potentially involved in pro-and anticancer, antioxidative and anti-hyperglycemic activities. Here, we investigated the anticancer efficiency of trilobatin on gefitinib resistant lung cancer cells. In this study, MTT assays, EdU incorporation assays, DAPI staining, tumor sphere formation assays, immunofluorescent staining and Western blot analysis were performed to explore the functional role of trilobatin on gefitinib resistant lung cancer cells. The results showed that trilobatin inhibits proliferation of gefitinib resistant lung cancer cells. In addition, the proportions of apoptotic cells were increased along with down-regulated expression levels of Bcl-2 and mitochondrial Cytochrome C while up-regulated Bax, Cleaved Caspase-3, -9, and cytosolic Cytochrome C expression. Moreover, trilobatin decreased tumor sphere formation and expression levels of multiple stemness markers (ALDH1, CD133, Nanog, and ABCG2) in gefitinib resistant lung cancer cells. Furthermore, investigation of the mechanism indicated that trilobatin suppressed activity of NF-κB via decreasing constitutive phosphorylation of NF-κB p65 and IκB-α in gefitinib resistant lung cancer cells. All these results indicate that trilobatin induces apoptosis and attenuates stemness phenotype of gefitinib resistant lung cancer cells, involved with, or partly, the suppression of NF-κB activity.
三叶亭碱是一种常见的黄酮类化合物，来源于 Rehd 叶。先前的报告表明，三叶亭碱可能参与了促癌和抗癌、抗氧化和抗高血糖作用。在这里，我们研究了三叶亭碱对吉非替尼耐药肺癌细胞的抗癌效率。在这项研究中，进行了 MTT 分析、EdU 掺入分析、DAPI 染色、肿瘤球形成分析、免疫荧光染色和 Western blot 分析，以探讨三叶亭碱对吉非替尼耐药肺癌细胞的功能作用。结果表明，三叶亭碱抑制吉非替尼耐药肺癌细胞的增殖。此外，随着 Bcl-2 和线粒体细胞色素 C 表达水平的下调，凋亡细胞的比例增加，而 Bax、Cleaved Caspase-3、-9 和细胞质细胞色素 C 的表达水平升高。此外，三叶亭碱降低了吉非替尼耐药肺癌细胞的肿瘤球形成和多个干性标志物（ALDH1、CD133、Nanog 和 ABCG2）的表达水平。此外，机制研究表明，三叶亭碱通过降低吉非替尼耐药肺癌细胞中 NF-κB p65 和 IκB-α的组成性磷酸化来抑制 NF-κB 的活性。所有这些结果表明，三叶亭碱诱导吉非替尼耐药肺癌细胞凋亡，并减弱其干性表型，这与 NF-κB 活性的抑制有关。
