天然产物研究与开发 ›› 2017, Vol. 29 ›› Issue (11): 1934-1939.doi: 10.16333/j.1001-6880.2017.11.020

• 开发研究 • 上一篇    下一篇

单宁酸联合顺铂增强肝癌HepG2细胞IRE1-XBP1通路的激活水平

耿娜娜1,2,吴明松1,2,3,郑翔3,杨蕾3,王宏阳3,李学英3*   

  1. 1遵义医学院口腔学院;2遵义医学院医学与生物学研究中心贵州省普通高等学校口腔疾病研究特色重点实验室;3遵义医学院医学遗传学教研室,遵义 563000
  • 出版日期:2017-11-29 发布日期:2017-11-30
  • 基金资助:

    贵州省教育厅特色药用资源研发创新团队(2013-15);贵州省科技厅资助(2014-7548);遵义医学院硕士启动基金(F-841);遵义医学院硕士启动基金(F-827)

Enhanced Activation of IRE1-XBP1 Pathway by Tannic Acid and Cis-dichlorodiamine Platinum in Human Hepatocellular Carcinoma HepG2 cells

GENG Na-na1,2, WU Ming-song1,2,3, ZHENG Xiang3, YANG Lei3, WANG Hong-yang3, LI Xue-ying3*   

  1. 1School of Stomatology,Zunyi Medical University; 2Special Key Laboratory of Oral Diseases Research,Higher Education institutions of Guizhou province;Research Center of Medicine and Biology of Zunyi Medical University; 3Medical Genetics Department of Zunyi Medical University,Zunyi 563000,China
  • Online:2017-11-29 Published:2017-11-30

摘要: 本文主要研究单宁酸(TA)联合顺铂(CDDP)对肝癌HepG2细胞内质网应激IRE1-XBP1通路的影响。用180 μM 单宁酸、0.9 μg/mL顺铂单独用药或者联合用药处理肝癌HepG2细胞24 h或48 h后,应用流式细胞技术测定HepG2细胞的凋亡率,实时荧光定量PCR技术(q-RT-PCR)、蛋白免疫印迹(western blot)技术检测IRE1α和XBP-1分子的表达水平。MTT结果显示,单宁酸和顺铂均能显著抑制HepG2细胞的生长,且均呈剂量性依赖;二者联合用药能够显著增加HepG2细胞的生长抑制率;流式细胞术结果显示,单宁酸与顺铂联合用药能够显著抑制HepG2细胞的增殖,并诱导细胞凋亡的发生;q-RT-PCR及Western blot结果显示,单宁酸与顺铂联合用药能显著上调细胞IRE1α和XBP-1的表达水平。结果表明单宁酸能够联合顺铂增强肝癌HepG2细胞内质网应激IRE1-XBP1通路的激活水平,提示IRE1-XBP1通路可能是单宁酸和顺铂协同抗肝癌HepG2细胞的分子机制之一。

关键词: 单宁酸, 顺铂, 肝癌, 内质网应激, 肌醇激酶1, X-盒结合蛋白1

Abstract: This study investigated the effect of tannic acid and cisplatin on IRE1-XBP1 pathway of endoplasmic reticulum stress in hepatocellular carcinoma HepG2 cells.HepG2 cells were cultured with 180 μM TA and/or 0.9 μg/mL CDDP for 24 h or 48 h.Then apoptosis rate was detected by flow cytometry and levels of IRE1α and XBP1 were analyzed by real-time fluorescence quantitative technology (q-RT-PCR) or western blot.MTT assay showed that TA or CDDP can inhibit HepG2 cells growth with dose dependence manner and TA combined with CDDP can significantly increase the growth inhibition rate of HepG2 cells.Flow cytometry results showed that tannic acid and cisplatin can significantly inhibit the proliferation of HepG2 cells and induce cell apoptosis.Q-RT-PCR and western blot results showed that tannic acid and cisplatin can significantly increase expression level of IRE1α and XBP-1.The results indicated that tannic acid can combine with cisplatin to increase the levels of IRE1-XBP1 pathway of endoplasmic reticulum stress in hepatocellular HepG2 cells,suggesting that the IRE1-XBP1 pathway may be one of the molecular mechanisms of synergistic anti-hepatocellular carcinoma effect of tannic acid and cisplatin on HepG2 cells.

Key words: tannic acid, cis-dichlorodiamine platinum, hepatocellular carcinoma, endoplasmic reticulum stress, inositol requiring enzymel 1, X box binding protein-1

中图分类号: 

R979.1+9