蜡菊亭抑制MITF/PGC-1α轴介导的MGC-803细胞线粒体有氧磷酸化

梁晓晖; 余明珠; 王萍; 张德高; 石海莲; 吴晓俊

doi:10.16306/j.1008-861x.2021.05.010

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蜡菊亭抑制MITF/PGC-1α轴介导的MGC-803细胞线粒体有氧磷酸化

实验研究 | 更新时间：2022-09-09

- 蜡菊亭抑制MITF/PGC-1α轴介导的MGC-803细胞线粒体有氧磷酸化
- Helichrysetin inhibits MITF/PGC-1α axis mediated mitochondrial oxidative phosphorylation in MGC-803 cells
- 上海中医药大学学报 2021年35卷第5期页码：61-66
- 作者机构：
  
  1.上海市复方中药重点实验室，教育部中药标准化重点实验室，国家中医药管理局中药新资源与品质评价重点研究室，上海中药标准化研究中心，上海中医药大学中药研究所（上海　201203）
  2.上海交通大学医学院附属新华医院崇明分院药剂科/药物临床试验机构办公室（上海　202150）
- 作者简介：
  
  梁晓晖，女，硕士，主要从事中药及其活性成分作用机制研究
  张德高，主管药师；E-mail：decaux@163.com。
  石海莲，研究员，硕士生导师；E-mail：shihailian2003@163.com
- 基金信息：
  
  上海市自然科学基金项目(21ZR1462800);国家自然科学基金资助项目(81603354);上海市教委预算内项目(2020LK014);上海中医药大学研究生创新创业能力培养项目(Y2020030;Y2021088);上海高校中药药效物质E研究院项目
- DOI：10.16306/j.1008-861x.2021.05.010
  中图分类号：
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梁晓晖, 余明珠, 王萍, 等. 蜡菊亭抑制MITF/PGC-1α轴介导的MGC-803细胞线粒体有氧磷酸化[J]. 上海中医药大学学报, 2021,35(5):61-66.

LIANG Xiaohui, YU Mingzhu, WANG Ping, et al. Helichrysetin inhibits MITF/PGC-1α axis mediated mitochondrial oxidative phosphorylation in MGC-803 cells[J]. Academic Journal of Shanghai University of Traditional Chinese Medicine, 2021,35(5):61-66.
梁晓晖, 余明珠, 王萍, 等. 蜡菊亭抑制MITF/PGC-1α轴介导的MGC-803细胞线粒体有氧磷酸化[J]. 上海中医药大学学报, 2021,35(5):61-66. DOI： 10.16306/j.1008-861x.2021.05.010.

LIANG Xiaohui, YU Mingzhu, WANG Ping, et al. Helichrysetin inhibits MITF/PGC-1α axis mediated mitochondrial oxidative phosphorylation in MGC-803 cells[J]. Academic Journal of Shanghai University of Traditional Chinese Medicine, 2021,35(5):61-66. DOI： 10.16306/j.1008-861x.2021.05.010.

摘要

目的：,2,考察蜡菊亭对人胃癌MGC-803细胞线粒体有氧磷酸化的影响，并探讨其分子机制。,方法：,2,①将细胞分为对照组和蜡菊亭不同浓度（10、20、40 μmol/L）组，分别给予相应干预。药物作用24、48 h后，试剂盒检测线粒体有氧磷酸化相关指标。②将细胞分为对照组和蜡菊亭（20 μmol/L）组，分别给予相应干预。药物作用12、24 h后，PCR检测过氧化物酶体增殖物活化受体γ共刺激因子-1α（,PGC-1α,）、黑色素细胞诱导转录因子（,MITF,）mRNA表达，Western blot检测PGC-1α蛋白表达。③将细胞分为对照组、蜡菊亭（20 μmol/L）组、PGC-1α激动剂（10 μmol/L）组、蜡菊亭+激动剂联用组，各组分别给予相应干预，处理细胞24 h后，CCK-8法检测各组细胞活力。,结果：,2,①与对照组相比，药物干预24 h后，蜡菊亭20 μmol/L组细胞基础呼吸和质子渗漏均受到抑制（,P,<,0.05，,P,<,0.01），蜡菊亭40 μmol/L组细胞基础呼吸、最大呼吸、质子渗漏、ATP生成和备用呼吸能力均受到抑制（,P,<,0.05，,P,<,0.01）；药物干预48 h后，蜡菊亭各浓度组细胞的基础呼吸、最大呼吸、质子渗漏和备用呼吸能力均受到抑制（,P,<,0.05，,P,<,0.01），蜡菊亭20、40 μmol/L组细胞ATP生成亦明显降低（,P,<,0.01）。②蜡菊亭（20 μmol/L）干预12、24 h后能够显著下调MGC-803细胞PGC-1α的mRNA和蛋白表达（,P,<,0.01）以及,MITF, mRNA表达（,P,<,0.01）。③蜡菊亭（20 μmol/L）能够显著降低MGC-803细胞活力（,P,<,0.01），但该作用可被PGC-1α激动剂拮抗，蜡菊亭+激动剂组的细胞活力明显高于蜡菊亭组（,P,<,0.01）。,结论：,2,蜡菊亭可能通过抑制MITF/PGC-1α轴，降低MGC-803细胞的线粒体有氧磷酸化，进而抑制肿瘤细胞活力。

Abstract

Objective:,2,To investigate the effects of helichrysetin on mitochondrial oxidative phosphorylation(OXPHOS) in human gastric cancer MGC-803 cells and explore its molecular mechanism.,Methods:,2,①The cells were divided into the control group and helichrysetin groups with different concentrations(10, 20, 40 μmol/L), which were treated with the corresponding intervention.After treatment for 24 and 48 hours, the related indexes of mitochondrial OXPHOS were detected by kits.②The cells were divided into the control group and helichrysetin(20 μmol/L) group, which were treated with the corresponding intervention.After treatment for 12 and 24 hours, the mRNA expressions of peroxisome proliferator-activated receptor γ coactivator-1α(,PGC-1α,) and melanocyte inducing transcription factor(,MITF,) were detected by PCR, and the protein expression of PGC-1α was detected by Western blot.③The cells were divided into the control group, helichrysetin(20 μmol/L) group, PGC-1α agonist(10 μmol/L) group and helichrysetin plus agonist group, which were treated with the corresponding intervention.After treatment for 24 hours, the cell viability was detected by CCK-8 assay.,Results:,2,①After drug intervention for 24 hours, compared with the control group, the basic respiration and proton leakage were inhibited in the helichrysetin 20 μmol/L group(,P,<,0.05,P,<,0.01), and the basic respiration, maximal respiration, proton leakage, ATP production and spare respiration capacity were inhibited in the helichrysetin 40 μmol/L group(,P,<,0.05,P,<,0.01) .After drug intervention for 48 hours, compared with the control group, the basal respiration, maximal respiration, proton leakage and spare respiration capacity were inhibited in the helichrysetin groups with different concentrations(,P,<,0.05,P,<,0.01), and the ATP production was also significantly decreased in the helichrysetin 20 and 40 μmol/L groups(,P,<,0.01) .②After treatment with helichrysetin at 20 μmol/L for 12 and 24 hours, the mRNA and protein expressions of PGC-1α and the mRNA expression of ,MITF, in MGC-803 cells were significantly down-regulated(,P,<,0.01) .③Helichrysetin at 20 μmol/L could significantly reduce the cell viability of MGC-803 cells(,P,<,0.01), but this effect could be antagonized by PGC-1α agonist, and the cell viability of the helichrysetin plus agonist group was obviously higher than that of the helichrysetin group(,P,<,0.01) .,Conclusion:,2,Helichrysetin may inhibit MITF/PGC-1α axis, reduce mitochondrial OXPHOS of MGC-803 cells, and then suppress the viability of tumor cells.

关键词

蜡菊亭胃癌线粒体有氧磷酸化细胞活力PGC-1α

Keywords

helichrysetingastric cancermitochondrial oxdative phosphorylationcell viabilityPGC-1α

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