Bernig Toralf, Ritz Stephanie, Brodt Grit, Volkmer Ines, Staege Martin Sebastian
Department of Pediatrics, Martin Luther University Halle-Wittenberg, Halle, Germany.
Department of Pediatrics, Martin Luther University Halle-Wittenberg, Halle, Germany
Anticancer Res. 2016 Aug;36(8):3905-15.
Glutathione-S-transferases (GSTs) are associated with multidrug resistance of tumor cells and are involved in drug detoxification and control of apoptosis. We analyzed the impact of GSTs on apoptosis of Hodgkin's lymphoma (HL) cells.
Expression of GST isoforms in HL cell lines was assessed by analysis of DNA microarray data and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The impact of the GST inhibitor ethacrynic acid (EA) on HL cell survival was analyzed in vitro.
DNA microarray analysis and qRT-PCR analysis demonstrated higher expression of GST isoforms in chemoresistant HL cells. Therefore, GSTs may contribute to chemoresistance of HL cells. Incubation of GST-expressing chemoresistant L-1236 HL cells with EA significantly enhanced the activity of cisplatin against these cells.
Our data suggest that the combined treatment with chemotherapy and GST inhibitors such as EA might be an interesting option for patients with chemoresistant HL.
谷胱甘肽 - S - 转移酶(GSTs)与肿瘤细胞的多药耐药性相关,参与药物解毒及细胞凋亡调控。我们分析了GSTs对霍奇金淋巴瘤(HL)细胞凋亡的影响。
通过DNA微阵列数据分析和定量逆转录 - 聚合酶链反应(qRT - PCR)评估HL细胞系中GST同工型的表达。体外分析GST抑制剂依他尼酸(EA)对HL细胞存活的影响。
DNA微阵列分析和qRT - PCR分析表明,化疗耐药的HL细胞中GST同工型表达较高。因此,GSTs可能促成HL细胞的化疗耐药性。用EA孵育表达GST的化疗耐药L - 1236 HL细胞,可显著增强顺铂对这些细胞的活性。
我们的数据表明,化疗与EA等GST抑制剂联合治疗可能是化疗耐药HL患者的一个有前景的选择。