果糖-1,6-二磷酸酶1抑制结肠癌SW480细胞的侵袭以及有氧糖酵解
详细信息    查看全文 | 推荐本文 |
  • 英文篇名:Fructose-1,6-bisphosphatase 1 inhibits invasion and aerobic glycolysis of colon cancer SW480 cells
  • 作者:郝杰 ; 陈建芳 ; 李甫 ; 欧娟娟 ; 梁后杰
  • 英文作者:HAO Jie;CHEN Jianfang;LI Fu;OU Juanjuan;LIANG Houjie;Department of Oncology,First Affiliated Hospital,Army Medical University ( Third Military Medical University);
  • 关键词:果糖1 ; 6二磷酸酶 ; 结肠癌 ; 侵袭 ; 有氧糖酵解
  • 英文关键词:fructose-1,6-bisphosphatase;;colon cancer;;invasion;;aerobic glycolysis
  • 中文刊名:DSDX
  • 英文刊名:Journal of Third Military Medical University
  • 机构:陆军军医大学(第三军医大学)第一附属医院肿瘤科;
  • 出版日期:2019-01-09 07:00
  • 出版单位:第三军医大学学报
  • 年:2019
  • 期:v.41;No.560
  • 基金:国家自然科学基金面上项目(81672941)~~
  • 语种:中文;
  • 页:DSDX201909003
  • 页数:6
  • CN:09
  • ISSN:50-1126/R
  • 分类号:15-20
摘要
目的探讨果糖-1,6-二磷酸酶1(fructose-1,6-bisphosphatase 1, FBP1)在结肠癌及其癌旁组织中的表达,以及在结肠癌侵袭及有氧糖酵解中的作用和机制。方法应用组织芯片技术结合免疫组织化学染色方法检测FBP1表达,对结果及临床病理学参数进行统计学分析;干扰结肠癌SW480细胞FBP1表达,CCK-8检测其细胞增殖,Transwell实验检测细胞侵袭能力,细胞能量代谢实验检测细胞糖酵解能力。结果 FBP1在80例结肠癌组织中高表达率显著低于80例癌旁肠黏膜组织(21.25%vs 86.25%,P<0.01);CCK-8检测结果显示FBP1可以抑制结肠癌SW480细胞的增殖能力(P<0.01); Transwell实验结果显示FBP1可以抑制SW480细胞的侵袭能力(P<0.01);细胞能量代谢实验结果显示FBP1可以抑制SW480的糖酵解水平。结论 FBP1蛋白在结肠癌组织中表达低于癌旁肠黏膜组织,其能抑制结肠癌SW480细胞的侵袭以及有氧糖酵解。
        Objective To determine the expression of fructose-1,6-bisphosphatase 1(FBP1) in colon cancer tissues, and investigate its roles and underlying mechanisms in the invasion and aerobic glycolysis of colon cancer cells. Methods The expression of FBP1 was detected by tissue microarray combined with immunohistochemical staining, and then the results were statistically analyzed with clinical pathological parameters. In the colon cancer SW480 cells with vector control, FBP1 overexpression or knock-down, CCK-8 assay was used to evaluate cell proliferation, Transwell chamber test was employed to detect their cell invasion ability, and cell energy metabolism test was applied to measure cell glycolysis. Results The higher expression of FBP1 in 80 cases of colon cancer tissues was significantly lower than that in 80 para-cancerous tissues(21.25% vs 86.25%, P<0.01). The results of CCK-8 assay showed that FBP1 inhibited the proliferation of SW480 cells(P<0.01). Transwell assay indicated that FBP1 inhibited the invasion of SW480 cells(P<0.01). Cell energy metabolism test showed that FBP1 suppressed the level of glycolysis in SW480 cells. Conclusion FBP1 is lowly expressed in colon cancer tissues compared to para-cancerous tissues. FBP1 inhibits migration, invasion and aerobic glycolysis of colon cancer SW480 cells.
引文
[1] BRAY F,FERLAY J,SOERJOMATARAM I,et al.Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2018,68(6):394-424.DOI:10.3322/caac.21492.
    [2] MARTINEZ-OUTSCHOORN U E,PEIRIS-PAGéS M,PESTELL R G,et al.Cancer metabolism:a therapeutic perspective[J].Nat Rev Clin Oncol,2017,14(1):11-13.DOI:10.1038/nrclinonc.2016.60.
    [3] LEVINE A J,PUZIO-KUTER A M.The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes[J].Science,2010,330(6009):1340-1344.DOI:10.1126/science.1193494.
    [4] WARBURG O.On the origin of cancer cells[J].Science,1956,123(3191):309-314.DOI:10.1126/science.123.3191.309.
    [5] SINGH S,HARMALKAR D S,CHOI Y,et al.Fructose-1,6-bisphosphatase inhibitors:a review of recent (2000-2017) advances and structure-activity relationship studies[J].Curr Med Chem,2018,25.DOI:10.2174/092986732566618083 1133734.
    [6] MOU J J,PENG J,SHI Y Y,et al.Mitochondrial DNA content reduction induces aerobic glycolysis and reversible resistance to drug-induced apoptosis in SW480 colorectal cancer cells[J].Biomed Pharmacother,2018,103:729-737.DOI:10.1016/j.biopha.2018.04.099.
    [7] DONG C,YUAN T,WU Y,et al.Loss of FBP1 by Snail-mediated repression provides metabolic advantages in basal-like breast cancer[J].Cancer Cell,2013,23(3):316-331.DOI:10.1016/j.ccr.2013.01.022.
    [8] HIRATA H,SUGIMACHI K,KOMATSU H,et al.Decreased expression of fructose-1,6-bisphosphatase associates with glucose metabolism and tumor progression in hepatocellular carcinoma[J].Cancer Res,2016,76(11):3265-3276.DOI:10.1158/0008-5472.Can-15-2601.
    [9] LI B,QIU B,LEE D S,et al.Fructose-1,6-bisphosphatase opposes renal carcinoma progression[J].Nature,2014,513(7517):251-255.DOI:10.1038/nature13557.
    [10] LI J,WANG Y,LI Q G,et al.Downregulation of FBP1 promotes tumor metastasis and indicates poor prognosis in gastric cancer via regulating epithelial-mesenchymaltransition[J].PLoS ONE,2016,11(12):e0167857.DOI:10.1371/journal.pone.0167857.
    [11] LIU G M,LI Q,ZHANG P F,et al.Restoration of FBP1 suppressed Snail-induced epithelial to mesenchymal transition in hepatocellular carcinoma[J].Cell Death Dis,2018,9(11):1132.DOI:10.1038/s41419-018-1165-x.
    [12] 林树海,蔡宗苇.同位素示踪技术定量分析肿瘤细胞中的代谢重编[J].色谱,2015,33(2):112-115.DOI:10.3724/SP.J.1123.2014.11011.LIN S H,CAI Z W.Isotopic tracing technique in quantitative analysis of metabolic reprogramming in tumor cells[J].Se Pu,2015,33(2):112-115.DOI:10.3724/SP.J.1123.2014.11011.
    [13] ZHANG J,WANG J,XING H,et al.Down-regulation of FBP1 by ZEB1-mediated repression confers to growth and invasion in lung cancer cells[J].Mol Cell Biochem,2016,411(1/2):331-340.DOI:10.1007/s11010-015-2595-8.
    [14] CHEN M,ZHANG J,LI N,et al.Promoterhypermethylation mediated downregulation of FBP1 in human hepatocellular carcinoma and colon cancer[J].PLoS ONE,2011,6(10):e25564.DOI:10.1371/journal.pone.0025564.
    [15] YANG J,JIN X,YAN Y,et al.Inhibiting histonedeacetylases suppresses glucose metabolism and hepatocellular carcinoma growth by restoring FBP1 expression[J].Sci Rep,2017,7:43864.DOI:10.1038/srep43864.
    [16] KONDAVEETI Y,GUTTILLA REED I K,WHITE B A.Epithelial-mesenchymal transition induces similar metabolic alterations in two independent breast cancer cell lines[J].Cancer Lett,2015,364(1):44-58.DOI:10.1016/j.canlet.2015.04.025.
    [17] HAM J,COSTA C,SANO R,et al.Exploitation of theapoptosis-primed state of MYCN-amplified neuroblastoma to develop a potent and specific targeted therapy combination[J].Cancer Cell,2016,29(2):159-172.DOI:10.1016/j.ccell.2016.01.002.
NGLC 2004-2010.National Geological Library of China All Rights Reserved.
Add:29 Xueyuan Rd,Haidian District,Beijing,PRC. Mail Add: 8324 mailbox 100083
For exchange or info please contact us via email.