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首页> 外文期刊>Oxidative Medicine and Cellular Longevity >Epigallocatechin-3-Gallate Enhances the Therapeutic Effects of Leptomycin B on Human Lung Cancer A549 Cells
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Epigallocatechin-3-Gallate Enhances the Therapeutic Effects of Leptomycin B on Human Lung Cancer A549 Cells

机译：Epigallocatechin-3-Gallate增强Leptomycin B对人肺癌A549细胞的治疗作用

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Our previous studies have shown Leptomycin B (LMB) is a promising antilung cancer drug. Epigallocatechin-3-gallate (EGCG) has antitumor properties but a debatable clinical application. The objective of this study is to evaluate the combination therapeutic effect of LMB and EGCG and its molecular mechanisms in human lung cancer A549 cells. Increased cytotoxicity was observed in LMB+EGCG-treated cells compared to LMB-treated cells. Elevated ROS was maximized 2 h after treatment, and LMB+EGCG-treated cells had higher ROS levels compared to LMB. N-Acetyl-L-cysteine (NAC) studies confirmed the oxidative role of LMB and/or EGCG treatment. In comparison to the control, CYP3A4, SOD, GPX1, and p21 mRNA expression levels were increased 7.1-, 2.0-, 4.6-, and 13.1-fold in LMB-treated cells, respectively, while survivin was decreased 42.6-fold. Additionally, these increases of CYP3A4, SOD, and GPX1 were significantly reduced, while p21 was significantly increased in LMB+EGCG-treated cells compared to LMB-treated cells. The qRT-PCR results for p21 and survivin were further confirmed by Western blot. Our study first shows that LMB produces ROS and is possibly metabolized by CYP3A4, GPX1, and SOD in A549 cells, and combination treatment of LMB and EGCG augments LMB-induced cytotoxicity through enhanced ROS production and the modulation of drug metabolism and p21/survivin pathways.
机译：我们以前的研究表明，Leptomycin B（LMB）是一种有前途的抗肺癌药物。表没食子儿茶素-3-没食子酸酯（EGCG）具有抗肿瘤特性，但在临床上仍有争议。这项研究的目的是评估LMB和EGCG在人肺癌A549细胞中的联合治疗作用及其分子机制。与LMB处理的细胞相比，在LMB + EGCG处理的细胞中观察到增加的细胞毒性。处理后2小时，ROS升高最大，与LMB相比，LMB + EGCG处理的细胞具有更高的ROS水平。 N-乙酰-L-半胱氨酸（NAC）研究证实了LMB和/或EGCG治疗的氧化作用。与对照组相比，在LMB处理的细胞中，CYP3A4，SOD，GPX1和p21 mRNA表达水平分别提高了7.1、2.0、4.6和13.1倍，而survivin降低了42.6倍。此外，与LMB处理的细胞相比，在LMB + EGCG处理的细胞中CYP3A4，SOD和GPX1的这些增加显着降低，而p21显着增加。 Western印迹进一步证实了p21和survivin的qRT-PCR结果。我们的研究首先表明LMB会产生ROS，并可能通过CYP3A4，GPX1和SOD在A549细胞中代谢，并且LMB和EGCG的联合治疗可通过增强ROS的产生，调节药物代谢和p21 / survivin途径来增强LMB诱导的细胞毒性。 。

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