Department of Clinical Biochemistry, Faculty of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Nutr Cancer. 2020;72(3):522-527. doi: 10.1080/01635581.2019.1636102. Epub 2019 Jul 10.
Glucosamine (GlcN) is a natural amino monosaccharide in the human body, and evidence of its anticancer effects is growing. In this study, we aimed to evaluate the effects of GlcN for its cytotoxicity, MDR reversal effects and inhibitory effects on function and expression of P-glycoprotein (P-gp) transporter in the daunorubicin-resistant human gastric cancer cells. Cell viability was measured by MTT assay to evaluate the cytotoxicity and multidrug resistance (MDR) reversal effects of GlcN. The effects of GlcN on function and mRNA expression level of P-gp transporter were assessed by flow cytometry and real-time RT-qPCR, respectively. Our results indicated that GlcN reduced the proliferation of human gastric cancer cell line EPG85-257 and its drug-resistant variant EPG85-257RD in a dose-dependent manner. GlcN (at the concentrations of 0.5 and 1 mM) also enhanced the sensitivity of EPG85-257RDB cells to daunorubicin. The cellular accumulation studies showed that GlcN inhibited efflux activity of P-gp and enhanced the mean fluorescent intensity of Rho123 while it had no effects on P-gp gene expression in these cells. This study suggested that the inhibition of P-gp activity is a novel mechanism of action by which GlcN could reverse MDR in EPG85-257RDB cells.
氨基葡萄糖（GlcN）是人体内天然存在的氨基酸单糖，其抗癌作用的证据越来越多。在这项研究中，我们旨在评估 GlcN 的细胞毒性、多药耐药（MDR）逆转作用及其对耐柔红霉素人胃癌细胞中 P-糖蛋白（P-gp）转运蛋白功能和表达的抑制作用。通过 MTT 测定法测量细胞活力，以评估 GlcN 的细胞毒性和多药耐药（MDR）逆转作用。通过流式细胞术和实时 RT-qPCR 分别评估 GlcN 对 P-gp 转运蛋白功能和 mRNA 表达水平的影响。我们的结果表明，GlcN 以剂量依赖性方式降低人胃癌细胞系 EPG85-257 及其耐药变体 EPG85-257RD 的增殖。GlcN（在 0.5 和 1mM 浓度下）还增强了 EPG85-257RDB 细胞对柔红霉素的敏感性。细胞积累研究表明，GlcN 抑制了 P-gp 的外排活性，增强了 Rho123 的平均荧光强度，而对这些细胞中的 P-gp 基因表达没有影响。这项研究表明，抑制 P-gp 活性是 GlcN 逆转 EPG85-257RDB 细胞多药耐药的一种新作用机制。
