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)
靳金美,女,硕士,主要从事中药及其活性成分作用机制研究
石海莲,研究员,硕士生导师;E-mail:shihailian2003@163.com。
张德高,主管药师;E-mail:decaux@163.com
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靳金美, 邱水平, 石海莲, 等. 小豆蔻明对人三阴性乳腺癌MDA-MB-231细胞葡萄糖摄取能力的影响[J]. 上海中医药大学学报, 2021,35(4):54-60.
JIN Jinmei, QIU Shuiping, SHI Hailian, et al. Effects of cardamonin on glucose uptake capacity in human triple negative breast cancer MDA-MB-231 cells[J]. Academic Journal of Shanghai University of Traditional Chinese Medicine, 2021,35(4):54-60.
靳金美, 邱水平, 石海莲, 等. 小豆蔻明对人三阴性乳腺癌MDA-MB-231细胞葡萄糖摄取能力的影响[J]. 上海中医药大学学报, 2021,35(4):54-60. DOI: 10.16306/j.1008-861x.2021.04.008.
JIN Jinmei, QIU Shuiping, SHI Hailian, et al. Effects of cardamonin on glucose uptake capacity in human triple negative breast cancer MDA-MB-231 cells[J]. Academic Journal of Shanghai University of Traditional Chinese Medicine, 2021,35(4):54-60. DOI: 10.16306/j.1008-861x.2021.04.008.
目的:,2,考察小豆蔻明对人三阴性乳腺癌MDA-MB-231细胞葡萄糖摄取能力的影响,并探讨其分子机制。,方法:,2,将MDA-MB-231细胞分为小豆蔻明不同浓度(0、10、20、40、80 μmol/L)组,分别予以相应浓度药物干预24 h。CCK-8法检测细胞活力,2-NBDG法检测细胞葡萄糖摄取能力,PCR法检测细胞葡萄糖转运体(,GLUT,)mRNA表达,Western blot法检测细胞GLUT蛋白表达。皮下接种MDA-MB-231细胞构建荷瘤裸鼠模型,小豆蔻明(0.3、1.0、3.0 mg/kg)腹腔注射给药4周后,分离荷瘤小鼠乳腺癌组织,Western blot法检测乳腺癌组织GLUT蛋白表达。,结果:,2,小豆蔻明(20、40、80 μmol/L)能剂量依赖性抑制MDA-MB-231细胞的活力(,P,<,0.01),且小豆蔻明(20 μmol/L)能够显著降低乳腺癌细胞的葡萄糖摄取能力(,P,<,0.05)。进一步研究发现,小豆蔻明(20 μmol/L)能够显著下调乳腺癌细胞,GLUT3,和,GLUT4, mRNA表达(,P,<,0.01);小豆蔻明(40 μmol/L)能够显著下调乳腺癌细胞GLUT3蛋白表达(,P,<,0.01),小豆蔻明(10、20、40 μmol/L)能够显著下调乳腺癌细胞GLUT4蛋白表达(,P,<,0.01),但对GLUT1蛋白表达无明显影响(,P,>,0.05)。小豆蔻明(0.3、1.0、3.0 mg/kg)能够显著降低荷瘤裸鼠乳腺癌组织GLUT1蛋白表达(,P,<,0.01),而小豆蔻明(1.0、3.0 mg/kg)能够显著下调GLUT3蛋白表达(,P,<,0.01)。,结论:,2,小豆蔻明可能通过下调GLUT mRNA和蛋白表达,降低人三阴性乳腺癌MDA-MB-231细胞的活力和葡萄糖摄取能力。
Objective:,2,To investigate the effects of cardamonin on the glucose uptake capacity in human triple negative breast cancer MDA-MB-231 cells and explore its molecular mechanism.,Methods:,2,MDA-MB-231 cells were divided into the cardamonin groups with different concentrations(0, 10, 20, 40, 80 μmol/L) .Each group was treated with cardamonin at the corresponding concentration for 24 hours.The cell viability was detected by CCK-8 assay.The glucose uptake capacity was evaluated by 2-NBDG assay.The mRNA expressions of glucose transporters(,GLUT,) were detected by PCR.The protein expressions of GULT were detected by Western blot.MDA-MB-231 cells were subcutaneously inoculated to construct tumor bearing nude mice model.After intraperitoneal injection of cardamonin(0.3, 1.0, 3.0 mg/kg) for 4 weeks, the breast cancer tissue of tumor bearing mice was isolated, and the expressions of GLUT proteins in the breast cancer tissue were detected by Western blot.,Results:,2,Cardamonin(20, 40, 80 μmol/L) significantly inhibited the viability of MDA-MB-231 cells in a dose-dependent manner(,P,<,0.01), and cardamonin at concentration of 20 μmol/L significantly reduced the glucose uptake capacity of breast cancer cells(,P,<,0.05) .Further studies showed that, cardamonin at concentration of 20 μmol/L significantly down-regulated the mRNA expressions of ,GLUT3, and ,GLUT4, in breast cancer cells(,P,<,0.01) .Cardamonin at concentration of 40 μmol/L significantly down-regulated the protein expression of GLUT3 in breast cancer cells(,P,<,0.01), cardamonin(10, 20, 40 μmol/L) significantly down-regulated the protein expression of GLUT4 in breast cancer cells(,P,<,0.01), but showed no obvious effect on GLUT1 protein expression(,P,>,0.05) .Cardamonin(0.3, 1.0, 3.0 mg/kg) significantly reduced the protein expression of GLUT1 in breast cancer tissue of tumor bearing mice(,P,<,0.01), while cardamonin(1.0, 3.0 mg/kg) significantly down-regulated the protein expression of GLUT3(,P,<,0.01) .,Conclusion:,2,Cardamonin may decrease the cell viability and glucose uptake capacity of human triple negative breast cancer MDA-MB-231 cells by down-regulating the mRNA and protein expressions of GLUT.
小豆蔻明乳腺癌细胞活力葡萄糖摄取葡萄糖转运体
cardamoninbreast cancercell viabilityglucose uptakeglucose transporter
CHEN W Q,ZHENG R S,BAADE P D,et al. Cancer statistics in China,2015[J]. CA Cancer J Clin,2016,66(2):115-132.
刘爽,关尚为,吴东媛,等.肿瘤分子靶向药物不良反应文献分析[J].中国药房,2014,25(38):3613-3616.
许爱玲,张文香,武芳.紫杉醇类药物治疗乳腺癌不良反应的观察与护理[J].山西职工医学院学报,2006,16(4):53-54.
谢嵩.抗肿瘤药物不良反应调查与分析[D].济南:山东大学,2008.
徐颖,孙强,沈松杰,等.乳腺癌常用靶向治疗药物的心血管不良反应[J].中华乳腺病杂志(电子版),2018,12(3):182-186.
廖明娟,陈红风.中医药对乳腺癌内分泌治疗不良反应的作用[C]//中华中医药学会.第十二次全国中医、中西医结合乳房病学术会议论文集.北京:中华中医药学会,2011.
HANAHAN D,WEINBERG R A. Hallmarks of cancer:the next generation[J]. Cell,2011,144(5):646-74.
DIAS A S,ALMEIDA C R,HELGUERO L A,et al. Metabolic crosstalk in the breast cancer microenvironment[J]. Eur J Cancer,2019,121:154-171.
王萍,石海莲,吴晓俊.中药草豆蔻抗肿瘤化学成分和作用机制研究进展[J].中国药理学与毒理学杂志,2017,31(9):880-888.
REN G Y,SUN A N,DENG C,et al. The anti-inflammatory effect and potential mechanism of cardamonin in DSS-induced colitis[J]. Am J Physiol Gastrointest Liver Physiol,2015,309(7):G517-G527.
牛培广,张钰璇,史道华.己糖激酶介导小豆蔻明改善血管平滑肌细胞糖代谢的作用[J].现代生物医学进展,2011,11(4):653-656.
DAMASKOS C,GARMPI A,NIKOLETTOS K,et al. Triple-Negative Breast Cancer:The Progress of Targeted Therapies and Future Tendencies[J]. Anticancer Res,2019,39(10):5285-5296.
LUO M,SHANG L,BROOKS M D,et al. Targeting Breast Cancer Stem Cell State Equilibrium Through Modulation of Redox Signaling[J]. Cell Metab,2018,28(1):69-86.
TANG Y,FANG Q,SHI D H,et al. mTOR inhibition of cardamonin on antiproliferation of A549 cells is involved in a FKBP12 independent fashion[J]. Life Sci,2014,99(1-2):44-51.
XUE Z G,NIU P G,SHI D H,et al. Cardamonin Inhibits Angiogenesis by mTOR Downregulation in SKOV3 Cells[J]. Planta Med,2016,82(1-2):70-75.
MI X G,SONG Z B,SUN L G,et al. Cardamonin inhibited cell viability and tumorigenesis partially through blockade of testes-specific protease 50-mediated nuclear factor-κB signaling pathway activation[J]. Int J Biochem Cell Biol,2016,73:63-71.
NIU P G,ZHANG Y X,SHI D H,et al. Cardamonin Inhibits Metastasis of Lewis Lung Carcinoma Cells by Decreasing mTOR Activity[J]. PLoS One,2015,10(5):e0127778.
PASCOAL A C,EHRENFRIED C A,LOPEZ B G,et al. Antiproliferative activity and induction of apoptosis in PC-3 cells by the chalcone cardamonin from Campomanesia adamantium(Myrtaceae)in a bioactivity-guided study[J]. Molecules,2014,19(2):1843-1855.
PARK S Y,GWAK J S,HAN S J,et al. Cardamonin suppresses the proliferation of colon cancer cells by promoting β-catenin degradation[J]. Biol Pharm Bull,2013,36(6):1040-1044.
PARK M K,JO S H,LEE H J,et al. Novel suppressive effects of cardamonin on the activity and expression of transglutaminase-2 lead to blocking the migration and invasion of cancer cells[J]. Life Sci,2013,92(2):154-160.
QIN Y,SUN C Y,LU F R,et al. Cardamonin exerts potent activity against multiple myeloma through blockade of NF-κB pathway in vitro[J]. Leuk Res,2012,36(4):514-520.
YADAV V R,PRASAD S,AGGARWAL B B. Cardamonin sensitizes tumor cells to TRAIL through ROS- and CHOP-mediated up-regulation of death receptors and down-regulation of survival proteins[J]. Br J Pharmacol,2012,165(3):741-753.
JIA D Y,TAN Y,LIU H J,et al. Cardamonin reduces chemotherapy-enriched breast cancer stem-like cells in vitro and in vivo[J]. Oncotarget,2016,7(1):771-785.
EL-NAGA R N. Pre-treatment with cardamonin protects against cisplatin-induced nephrotoxicity in rats:impact on NOX-1,inflammation and apoptosis[J]. Toxicol Appl Pharmacol,2014,274(1):87-95.
LEE J Y,YESILKANAL A E,WYNNE J P,et al. Effective breast cancer combination therapy targeting BACH1 and mitochondrial metabolism[J]. Nature,2019,568(7751):254-258.
ARORA R,SCHMITT D,KARANAM B,et al. Inhibition of the Warburg effect with a natural compound reveals a novel measurement for determining the metastatic potential of breast cancers[J]. Oncotarget,2015,6(2):662-678.
JIN J M,QIU S P,WANG P,et al. Cardamonin inhibits breast cancer growth by repressing HIF-1α-dependent metabolic reprogramming[J]. J Exp Clin Cancer Res,2019,38(1):377.
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