大黄素通过下调Pgp增强非小细胞肺癌对顺铂的敏感性。
Emodin enhances cisplatin sensitivity in non-small cell lung cancer through Pgp downregulation.
作者信息
Peng Shuai, Wang Jincheng, Lu Chang, Xu Zelin, Chai Jing-Jing, Ke Qing, Deng Xin-Zhou
机构信息
Department of Clinical Medicine, Fourth Clinical College, Shiyan, Hubei 442000, P.R. China.
Department of Clinical Medicine, Institute of Medicine and Nursing, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
出版信息
Oncol Lett. 2021 Mar;21(3):230. doi: 10.3892/ol.2021.12491. Epub 2021 Jan 26.
Cisplatin resistance is one of the main causes of chemotherapy failure and tumor progression in non-small cell lung cancer (NSCLC). Emodin has been demonstrated to induce NSCLC cell apoptosis and act as a potential cancer therapeutic agent. However, whether emodin could affect NSCLC cell sensitivity toward cisplatin remains unclear. The present study aimed to determine the effect of emodin and cisplatin combination on the chemosensitivity of NSCLC cells. A549 and H460 cells were treated with different concentrations of cisplatin and/or emodin. Cell Counting Kit-8, fluorescence microscopy, immunofluorescence assays and flow cytometry were used to determine cell proliferation, drug efflux, DNA damage level and cell apoptosis, respectively. P-glycoprotein (Pgp) and multidrug resistance-associated protein 1 (MRP1) expression was detected by western blotting. The results demonstrated that emodin and cisplatin inhibited the proliferation of A549 and H460 cells. Furthermore, emodin inhibited the drug efflux in A549 and H460 cells in a dose-dependent manner. In addition, emodin enhanced cisplatin-induced apoptosis and DNA damage in A549 and H460 cells. Emodin also decreased Pgp expression in A549 and H460 cells in a dose-dependent manner; however, it had no effect on MRP1 expression. Taken together, the results from the present study demonstrated that emodin can increase A549 and H460 cell sensitivity to cisplatin by inhibiting Pgp expression. Emodin may therefore be considered as an effective adjuvant for cisplatin treatment.
顺铂耐药是导致非小细胞肺癌(NSCLC)化疗失败和肿瘤进展的主要原因之一。大黄素已被证明可诱导NSCLC细胞凋亡,并作为一种潜在的癌症治疗药物。然而,大黄素是否会影响NSCLC细胞对顺铂的敏感性仍不清楚。本研究旨在确定大黄素与顺铂联合使用对NSCLC细胞化疗敏感性的影响。用不同浓度的顺铂和/或大黄素处理A549和H460细胞。分别使用细胞计数试剂盒-8、荧光显微镜、免疫荧光分析和流式细胞术来测定细胞增殖、药物外排、DNA损伤水平和细胞凋亡。通过蛋白质印迹法检测P-糖蛋白(Pgp)和多药耐药相关蛋白1(MRP1)的表达。结果表明,大黄素和顺铂抑制了A549和H460细胞的增殖。此外,大黄素以剂量依赖性方式抑制A549和H460细胞中的药物外排。此外,大黄素增强了顺铂诱导的A549和H460细胞凋亡和DNA损伤。大黄素还以剂量依赖性方式降低A549和H460细胞中Pgp的表达;然而,它对MRP1的表达没有影响。综上所述,本研究结果表明,大黄素可通过抑制Pgp表达来增加A549和H460细胞对顺铂的敏感性。因此,大黄素可被视为顺铂治疗的有效佐剂。
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