Ho Chun-Te, Shang Hung-Sheng, Chang Jin-Biou, Liu Jun-Jen, Liu Tsan-Zon
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Department of Pathology, National Defense Medical Center, Division of Clinical Pathology, Tri-Service General Hospital, Taipei, Taiwan.
Oncotarget. 2015 Sep 22;6(28):26104-18. doi: 10.18632/oncotarget.4422.
Patients with hepatocellular carcinoma (HCC) are prone to folate deficiency (FD). Here we showed that, in cell line-specific manner, FD caused resistance to FD-induced oxidative stress and multi-drug resistance (MDR). This resistance was due to upregulation of glucose-regulated protein 78 (GRP78) and Survivin. Using siRNA and Epigallocatechin gallate (EGCG), we found that GRP78 and Survivin cooperatively conferred MDR by decreasing FD-induced ROS generation. Our data showed that FD increases GRP78 and Survivin, which serve as ROS inhibitors, causing MDR in HCC. We suggest that folate supplementation may enhance the efficacy of chemotherapy.
肝细胞癌（HCC）患者容易出现叶酸缺乏（FD）。在此我们表明，以细胞系特异性方式，FD导致对FD诱导的氧化应激和多药耐药性（MDR）产生抗性。这种抗性归因于葡萄糖调节蛋白78（GRP78）和生存素的上调。使用小干扰RNA（siRNA）和表没食子儿茶素没食子酸酯（EGCG），我们发现GRP78和生存素通过减少FD诱导的活性氧（ROS）生成协同赋予MDR。我们的数据表明，FD增加了作为ROS抑制剂的GRP78和生存素，从而导致HCC中的MDR。我们建议补充叶酸可能会增强化疗效果。
