Department of Gastroenterology, The Second Affiliated Hospital, University of South China, Hengyang, Hunan, China.
Am J Med Sci. 2012 May;343(5):382-7. doi: 10.1097/MAJ.0b013e31822f3c63.
To explore the mechanisms of rosiglitazone (ROS), a selective peroxisome proliferator-activated receptor gamma ligand, in reversing mitomycin C (MMC) resistance in a human drug-resistant gastric cancer cell line.
The vincristine-resistant human gastric cancer cell line SGC7901/VCR and its parental cell line SGC7901 were treated with ROS, MMC (negative control), cyclosporine A+MMC (positive control) or ROS+MMC. A tetrazolium blue (methyl thiazolyl tetrazolium) assay was used to evaluate the sensitivity to these treatments. Flow cytometry analysis and acridine orange-ethidium bromide (AO-EB) fluorescent staining were used to determine the effects of ROS on MMC-induced apoptosis. Reverse transcription polymerase chain reaction and western blotting were used to measure the expression of multidrug resistant 1 (MDR1), Livin and P-glycoprotein (P-gp).
ROS administration dose dependently increased the reversal index in MMC-treated SCG7901/VCR cells. ROS increased apoptosis in SGC7901/VCR cells compared with the blank group and MMC group. ROS+MMC also increased apoptosis in SGC7901/VCR cells compared with other groups (P < 0.05 or P < 0.01). The mRNA expression of MDR1 and Livin and the protein expression of P-gp in SGC7901/VCR cells were significantly higher than those in SGC7901 cells (P < 0.01). However, ROS or ROS+MMC treatment markedly upregulated the mRNA expression of MDR1 and Livin and the protein expression of P-gp in SGC7901/VCR cells (P < 0.01).
ROS reverses MMC resistance in human gastric cancer SGC7901/VCR cells by reducing expression of MDR1, Livin and P-gp and increasing apoptosis.
探索罗格列酮（ROS），一种选择性过氧化物酶体增殖物激活受体γ配体，逆转人耐药胃癌细胞系中丝裂霉素 C（MMC）耐药的机制。
用 ROS、MMC（阴性对照）、环孢素 A+MMC（阳性对照）或 ROS+MMC 处理长春新碱耐药人胃癌细胞系 SGC7901/VCR 及其亲本细胞系 SGC7901。四唑蓝（甲基噻唑基四唑）法评估这些处理的敏感性。流式细胞术分析和吖啶橙-溴化乙锭（AO-EB）荧光染色用于确定 ROS 对 MMC 诱导的凋亡的影响。逆转录聚合酶链反应和蛋白质印迹用于测量多药耐药 1（MDR1）、Livin 和 P-糖蛋白（P-gp）的表达。
ROS 给药剂量依赖性地增加了 MMC 处理的 SGC7901/VCR 细胞的逆转指数。与空白组和 MMC 组相比，ROS 增加了 SGC7901/VCR 细胞的凋亡。与其他组相比，ROS+MMC 也增加了 SGC7901/VCR 细胞的凋亡（P<0.05 或 P<0.01）。SGC7901/VCR 细胞中 MDR1、Livin 的 mRNA 表达和 P-gp 的蛋白表达明显高于 SGC7901 细胞（P<0.01）。然而，ROS 或 ROS+MMC 处理显著上调了 SGC7901/VCR 细胞中 MDR1、Livin 的 mRNA 表达和 P-gp 的蛋白表达（P<0.01）。
ROS 通过降低 MDR1、Livin 和 P-gp 的表达并增加凋亡来逆转人胃癌 SGC7901/VCR 细胞中 MMC 的耐药性。
