[1]徐 强,宋 杰,许 敏,等.M2型丙酮酸激酶同工酶表达对肝细胞癌化疗敏感性的影响 [J].介入放射学杂志,2019,28(09):855-860.
 XU Qiang,SONG Jie,XU Min,et al.Effect of PKM2 expression on the chemosensitivity of hepatocellular carcinoma[J].journal interventional radiology,2019,28(09):855-860.
点击复制

M2型丙酮酸激酶同工酶表达对肝细胞癌化疗敏感性的影响
()

PDF下载中关闭

分享到:

《介入放射学杂志》[ISSN:1008-794X/CN:31-1796/R]

卷:
28
期数:
2019年09期
页码:
855-860
栏目:
实验研究
出版日期:
2019-09-25

文章信息/Info

Title:
Effect of PKM2 expression on the chemosensitivity of hepatocellular carcinoma
作者:
徐 强 宋 杰 许 敏 安天志 王黎洲 李 兴 周 石
Author(s):
XU Qiang SONG Jie XU Min AN Tianzhi WANG Lizhou LI Xing ZHOU Shi.
School of Medical Imaging, Guizhou Medical University, Guiyang, Guizhou Province 550004, China
关键词:
【关键词】 肝细胞癌 M2型丙酮酸激酶同工酶 化学敏感性 有氧糖酵解 细胞凋亡
文献标志码:
A
摘要:
【摘要】 目的 研究M2型丙酮酸激酶同工酶(PKM2)对肝癌细胞HepG2增殖、迁移、侵袭和凋亡的影响,探讨PKM2表达对肝细胞癌(HCC)化疗敏感性的影响。方法 采用蛋白印迹和实时定量聚合酶链反应(RT- qPCR)检测正常肝细胞株HL- 7702和肝癌细胞株HepG2中PKM2蛋白和mRNA表达。构建靶向PKM2基因重组质粒(PKM2- siRNA)和对照质粒(siRNA- NC),并转染至HepG2细胞中,蛋白印迹和qRT- PCR检测PKM2敲低情况。细胞克隆形成、Transwell趋化和TUNEL法分析PKM2表达对细胞增殖、迁移、侵袭和凋亡的影响。不同浓度多柔比星(DOX)处理各组细胞后,CCK- 8和TUNEL法检测细胞活性和凋亡。 结果 HepG2细胞株中PKM2蛋白和mRNA表达与HL- 7702相比显著上调[mRNA(1.01±0.01)%对(5.04±0.02)%,蛋白(1.34±0.04)%对(4.03±0.02)%,P<0.05]。PKM2在PKM2- siRNA转染HepG2细胞中表达在转录和翻译水平显著降低,细胞克隆形成率、细胞侵袭数均低于空白转染组和转染siRNA- NC对照组,细胞凋亡率高于空白转染组和转染siRNA- NC对照组,DOX半抑制浓度(IC50)为7.25 μg/mL,转染siRNA- NC对照组为18.51 μg/mL。随着DOX给药浓度增加,细胞凋亡率显著增加。转染PKM2- siRNA细胞组凋亡数明显高于转染siRNA- NC对照组(P<0.05)。 结论 PKM2在人肝癌细胞株HepG2中高表达。敲低PKM2表达可抑制细胞增殖、迁移和侵袭,促进细胞凋亡,增强对DOX化疗敏感性。PKM2可能是HCC治疗的潜在靶点。

参考文献/References:

1 Torre LA Bray F Siegel RL et al. Global cancer statistics 2012J. CA Cancer J Clin 2015 65 87-108.

2 El- Serag HB. Hepatocellular carcinomaJ. N Engl J Med 2011 365 1118-1127.

3 Luo W Semenza GL. Pyruvate kinase M2 regulates glucose metabolism by functioning as a coactivator for hypoxia-inducible factor 1 in cancer cellsJ. Oncotarget 2011 2 551-556.

4 Israelsen WJ Dayton TL Davidson SM et al. PKM2 isoform-specific deletion reveals a differential requirement for pyruvate kinase in tumor cellsJ. Cell 2013 155 397- 409.

5 Liu WR Tian MX Yang LX et al. PKM2 promotes metastasis by recruiting myeloid- derived suppressor cells and indicates poor prognosis for hepatocellular carcinomaJ. Oncotarget 2015 6 846-861.

6 Yang W Xia Y Ji H et al. Nuclear PKM2 regulates β- catenin transactivation upon EGFR activationJ. Nature 2011 480 118-122.

7 Yuan C Li Z Wang Y et al. Overexpression of metabolic markers PKM2 and LDH5 correlates with aggressive clinicopath-ological features and adverse patient prognosis in tongue cancerJ. Histopathology 2014 65 595- 605.

8 Qiuran XU Xin L Xin Z et al. PKM2 regulates Gli1 expression in hepatocellular carcinomaJ. Oncol Lett 2014 8 1973-1979.

9 Bluemlein K Grüning NM Feichtinger RG et al. No evidence for a shift in pyruvate kinase PKM1 to PKM2 expression during tumorigenesisJ. Oncotarget 2011 2 393- 400.

10 Feng C Gao Y Wang C et al. Aberrant overexpression of pyruvate kinase M2 is associated with aggressive tumor features and the BRAF mutation in papillary thyroid cancerJ. J Clin Endocrinol Metab 2013 98 E1524- E1533.

11 Christofk HR Vander Heiden MG Harris MH et al. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growthJ. Nature 2008 452 230-233.

12 Xu Q Zhang M Tu J et al. MicroRNA-122 affects cell aggressiveness and apoptosis by targeting PKM2 in human hepatocellular carcinomaJ. Oncol Rep 2015 34 2054-2064.

13 东, 陈奕霖, 付斯瑜, 等. 三氧化二砷联合TACE治疗中晚期原发性肝癌疗效的meta分析[J]. 介入放射学杂志, 2018 27 523-529

14 张为家, 爽, 苏小岩, 等. β- catenin介导乳腺癌细胞多柔比星耐药实验研究[J]. 中华肿瘤防治杂志, 2018 25 232-237

15 Li SL Ye F Cai WJ et al. Quantitative proteome analysis of multidrug resistance in human ovarian cancer cell lineJ. J Cell Biochem 2010 109 625- 633.

16 Shi HS Li D Zhang J et al. Silencing of pkm2 increases the efficacy of docetaxel in human lung cancer xenografts in miceJ. Cancer Sci 2010 101 1447-1453.

17 Gines A Bystrup S Ruiz de Porras V et al. PKM2 subcellular localization is involved in oxaliplatin resistance acquisition in HT29 human colorectal cancer cell linesJ. PLoS One 2015 10 e0123830.

 

相似文献/References:

[1]姚雪松,李 槐.不可手术切除的肝细胞癌的疗效评价标准——改良RECIST标准更可靠[J].介入放射学杂志,2012,(03):177.
 . Therapeutic evaluation criterion of inoperable hepatocellular carcinomas: modified RECIST as a more reliable standard[J].journal interventional radiology,2012,(09):177.
[2]梁茂全,苏洪英. 肝癌化疗栓塞前后甲胎蛋白变化模式的临床意义[J].介入放射学杂志,2012,(04):333.
 .The transformation pattern of serum аfetoprotein after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma: its clinical significance [J].journal interventional radiology,2012,(09):333.
[3]孙 磊,施海彬,刘 圣,等.肝细胞癌肝动脉门静脉分流形成的相关因素分析[J].介入放射学杂志,2012,(03):206.
 ,,et al.The factors related to the formation of arterioportal shunting in patients with hepatocellular carcinomas [J].journal interventional radiology,2012,(09):206.
[4]沈海洋,刘瑞宝,刘 岩,等. 肝右叶前、后段原发性肝癌TACE后VEGF及CD34的表达水平 ;[J].介入放射学杂志,2012,(06):469.
 SHEN Hai- yang,LIU Rui- bao,LIU Yan,et al. The expression levels of vascular endothelial growth factor and CD34 in residual cancerous tissues of primary hepatocellular carcinoma located at anterior and posterior segments of right lobe liver after TACE[J].journal interventional radiology,2012,(09):469.
[5]李晓峰,钱国军,张 磊,等. 微波高功率条件下消融原发性肝癌的初步研究[J].介入放射学杂志,2011,(12):974.
 LI Xiao-feng,QIAN Guo-jun,ZHANG Lei,et al.Microwave ablation with high output power for the treatment of hepatocellular carcinoma: a preliminary study[J].journal interventional radiology,2011,(09):974.
[6]彭辽河,胡晓燕,李 杰,等. 18F-FDG PET/CT显像在肝细胞癌TACE术后残留或复发病灶检出中的应用价值[J].介入放射学杂志,2012,(08):636.
 PENG Liao- he,HU Xiao- yan,LI Jie,et al. Clinical application of 18F- FDG PET/CT imaging in detecting residual lesions or recurrence foci of hepatocellular carcinoma after TACE treatment[J].journal interventional radiology,2012,(09):636.
[7]陆小华,朱小庆,茅国新.肝细胞癌相关单核苷酸多态性的研究进展[J].介入放射学杂志,2013,(06):520.
 LU Xiao? hua,ZHU Xiao? qing,MAO Guo? xin.. Hepatocellular carcinoma?蛳 related single nucleotide polymorphisms: recent advances in research[J].journal interventional radiology,2013,(09):520.
[8]姚雪松,闫 东,曾辉英,等.TACE联合索拉非尼治疗不能手术切除肝细胞癌介入治疗间隔时间的分析[J].介入放射学杂志,2014,(09):769.
 YAO Xue song,YAN Dong,ZENG Hui ying,et al.TACE combined with sorafenib for inoperable hepatocellular carcinoma: analysis of treatment interval[J].journal interventional radiology,2014,(09):769.
[9]姚雪松,闫 东,曾辉英,等. TACE联合索拉非尼治疗不能手术切除肝细胞肝癌50例[J].介入放射学杂志,2013,(05):381.
 YAO Xue? song,YAN Dong,ZENG Hui? ying,et al. Ttransarterial chemoembolization combined with sorafenib for inoperable hepatocellular carcinoma: a clinical analysis of 50 cases[J].journal interventional radiology,2013,(09):381.
[10]赵 松,陈学春,龙清云,等. 经肝动脉化疗栓塞联合射频消融治疗肝细胞癌疗效荟萃分析[J].介入放射学杂志,2013,(11):908.
 ZHAO Song,CHEN Xue? chun,LONG Qing? yun,et al. Transcatheter arterial chemoembolization combined with radiofrequency ablation for the treatment of hepatocellular carcinoma: a systematic review and Meta analysis[J].journal interventional radiology,2013,(09):908.

备注/Memo

备注/Memo:
(收稿日期:2018-10-17)

(本文编辑:边 佶)
更新日期/Last Update: 2019-09-24