[1]杨大鹏,宦洪波,张亮,等.去甲肾上腺素通过PI3K/Akt信号通路上调Sox4表达促进肝癌细胞增殖[J].第三军医大学学报,2017,39(09):821-826.
 Yang Dapeng,Huan Hongbo,Zhang Liang,et al.Norepinephrine promotes proliferation of hepatocellular carcinoma cells through enhancing Sox4 expression via PI3K/Akt signal pathway[J].J Third Mil Med Univ,2017,39(09):821-826.
点击复制

去甲肾上腺素通过PI3K/Akt信号通路上调Sox4表达促进肝癌细胞增殖(/HTML )
分享到:

《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
39卷
期数:
2017年第09期
页码:
821-826
栏目:
基础医学
出版日期:
2017-05-15

文章信息/Info

Title:
Norepinephrine promotes proliferation of hepatocellular carcinoma cells through enhancing Sox4 expression via PI3K/Akt signal pathway
作者:
杨大鹏宦洪波张亮温旭东吴黎雳夏锋
第三军医大学西南医院全军肝胆外科研究所
Author(s):
Yang Dapeng Huan Hongbo Zhang Liang Wen Xudong Wu Lili Xia Feng

Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China

关键词:
肝癌细胞增殖去甲肾上腺素Sox4自我更新
Keywords:
proliferation in hepatocellular carcinoma cells norepinephrine Sox4 self-renew
分类号:
R730.23; R735.7; R977.11
文献标志码:
A
摘要:

目的      探讨去甲肾上腺素对肝癌细胞自我更新能力的影响及其分子机制。方法      实时荧光定量PCR和Western blot检测去甲肾上腺素对肝癌细胞(Huh7、PLC)中CD133表达水平的影响;肿瘤细胞球形成实验以及克隆形成实验检测去甲肾上腺素和哌唑嗪对肝癌细胞自我更新能力的作用;实时荧光定量PCR和Western blot检测去甲肾上腺素(10 μmol/L)和哌唑嗪(5 μmol/L)对肝癌细胞中干性相关基因表达的影响,并检测相关的信号通路。结果      去甲肾上腺素使Huh7和PLC肝癌细胞中的CD133表达升高;去甲肾上腺素处理Huh7和PLC肝癌细胞后的成球率较对照组明显上升,哌唑嗪处理后明显降低(P<0.05);在克隆形成实验中,去甲肾上腺素处理Huh7和PLC肝癌细胞的后,克隆形成率高于哌唑嗪组和对照组(P<0.05);与对照组和哌唑嗪组相比,去甲肾上腺素组中Sox4基因表达明显升高,同时p-Akt表达相较于哌唑嗪和对照组相比也明显上调(P<0.05)。结论      去甲肾上腺素激动肝癌细胞中α肾上腺素能受体, 通过激活PI3K/Akt信号通路上调肝癌细胞中Sox4基因表达,从而提高肝癌细胞自我更新的能力。

Abstract:

Objective       To determine the effect of norepinephrine on self-renewal capacity in hepatocellular carcinoma (HCC) cells and investigate the molecular mechanism. Methods      Quantitative RT-PCR and Western blotting were used to detect the expression level of CD133 in the HCC cell lines Huh7 and PLC after the treatment of 10 μmol/L norepinephrine. Sphere and clone formation assays were used to investigate the impact of norepinephrine on self-renewal capacity of HCC cells. The effects of norepinephrine (10 μmol/L) and prazosin (5 μmol/L) on the expression of stem related genes and signal pathways were detected by RT-PCR and Western blotting. Results      Norepinephrine promoted the expression of CD133 in Huh7 and PLC cells. Norepinephrine facilitated sphere and clone formation in the 2 cell lines, and prazosin blocked the effect of norepinephrine (P<0.05). There were more sphere and clone formation in the cells after norepinephrine treatment than control cells and prazosin group (P<0.05). Higher level of Sox4 and up-regulation of p-Akt were observed in the norepinephrine-treated cells than prazosin-treated and control HCC cells (P<0.05). Conclusion      Norepinephrine activates α-adrenergic receptor and up-regulates Sox4 expression via activating PI3K/Akt signal pathway, and thus improves self-renewal capacity in HCC cells.

参考文献/References:

[1]Chen W, Zheng R, Baade P D, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132. DOI:10.3322/caac.21338.
[2]Ferlay J, Shin H R, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008[J]. Int J Cancer, 2010, 127(12): 2893-2917. DOI:10.1002/ijc.25516.
[3]Andoniadou C L, Matsushima D, Mousavy Gharavy S N, et al. Sox2(+) stem/progenitor cells in the adult mouse pituitary support organ homeostasis and have tumor-inducing potential[J]. Cell Stem Cell, 2013, 13(4): 433-445. DOI:10.1016/j.stem.2013.07.004.
[4]Ying Z, Li Y, Wu J, et al. Loss of miR-204 expression enhances glioma migration and stem celllike phenotype[J]. Cancer Res, 2013, 73(2): 990-999. DOI:10.1158/0008-5472.CAN-12-2895.
[5]Roche K C, Gracz A D, Liu X F, et al. SOX9 maintains reserve stem cells and preserves radioresistance in mouse small intestine[J]. Gastroenterology, 2015, 149(6): 1553-1563.e10. DOI:10.1053/j.gastro.2015.07.004.
[6]Chai S, Ng K Y, Tong M, et al. Octamer 4/microRNA-1246 signaling axis drives Wnt/β-catenin activation in liver cancer stem cells[J]. Hepatology, 2016, 64(6):2062-2076. DOI:10.1002/hep.28821.
[7]Zhou X, Tan M, Nyati M K, et al. Blockage of neddylation modification stimulates tumor sphere formation in vitro and stem cell differentiation and wound healing in vivo[J]. Proc Natl Acad Sci U S A, 2016, 113(21): E2935-E2944. DOI:10.1073/pnas.1522367113.
[8]Ondicova K, Mravec B. Role of nervous system in cancer aetiopathogenesis[J]. Lancet Oncol, 2010, 11(6): 596-601. DOI:10.1016/S1470-2045(09)703377.
[9]Batty M, Pugh R, Rathinam I, et al. The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers[J]. Int J Mol Sci, 2016, 17(8): 1339. DOI:10.3390/ijms17081339.
[10]Lamkin D M, Sung H Y, Yang G S, et al. α2-Adrenergic blockade mimics the enhancing effect of chronic stress on breast cancer progression[J]. Psychoneuroendocrinology, 2015, 51: 262-270. DOI:10.1016/j.psyneuen.2014.10.004.
[11]Yeo J H, Yoon S Y, Kim S J, et al. Clonidine, an alpha-2 adrenoceptor agonist relieves mechanical allodynia in oxaliplatin-induced neuropathic mice; potentiation by spinal p38 MAPK inhibition without motor dysfunction and hypotension[J]. Int J Cancer, 2016, 138(10): 2466-2476. DOI:10.1002/ijc.29980.
[12]Morelli M B, Amantini C, Nabissi M, et al. Cross-talk between alpha1D-adrenoceptors and transient receptor potential vanilloid type 1 triggers prostate cancer cell proliferation[J]. BMC Cancer, 2014, 14(1). DOI:10.1186/1471-2407-14-921.
[13]Magnon C, Hall S J, Lin J, et al. Autonomic nerve development contributes to prostate cancer progression[J]. Science, 2013,341(6142):1236361. DOI:10.1126/science.1236361.
[14]Xia M, Tong J H, Zhou Z Q, et al. Tramadol inhibits proliferation, migration and invasion via α2adrenoceptor signaling in breast cancer cells[J]. Eur Rev Med Pharmacol Sci, 2016, 20(1): 157-165.
[15]Fitzgerald P J. Is norepinephrine an etiological factor in some types of cancer[J]. Int J Cancer, 2009, 124(2): 257-263. DOI:10.1002/ijc.24063.
[16]Huan H B, Wen X D, Chen X J, et al. Sympathetic nervous system promotes hepatocarcinogenesis by modulating inflammation through activation of alpha1-adrenergic receptors of Kupffer cells[J]. Brain Behav Immun, 2017, 59: 118-134. DOI:10.1016/j.bbi.2016.08.016.
[17]Ma S, Chan K W, Hu L, et al. Identification and characterization of tumorigenic liver cancer stem/progenitor cells[J]. Gastroenterology, 2007, 132(7): 2542-2556. DOI:10.1053/j.gastro.2007.04.025.
[18]Bilir B, Osunkoya A O, Wiles W G 4th, et al. SOX4 Is Essential for Prostate Tumorigenesis Initiated by PTEN Ablation[J]. Cancer Res, 2016, 76(5): 1112-1121. DOI:10.1158/0008-5472.CAN-15-1868.
[19]Chen Z Z, Huang L, Wu Y H, et al. LncSox4 promotes the self-renewal of liver tumour-initiating cells through Stat3-mediated Sox4 expression[J]. Nat Commun, 2016, 7: 12598. DOI:10.1038/ncomms12598.
[20]Yin C. Molecular mechanisms of Sox transcription factors during the development of liver, bile duct, and pancreas[J]. Semin Cell Dev Biol, 2017, 63:68-78. DOI:10.1016/j.semcdb.2016.08.015.
[21]Cheung M, Abu-Elmagd M, Clevers H, et al. Roles of Sox4 in central nervous system development[J]. Brain Res Mol Brain Res, 2000, 79(1/2): 180-191. DOI:10.1016/s0169-328x(00)00109-1.
[22]Lee H, Goodarzi H, Tavazoie S F, et al. TMEM2 Is a SOX4-Regulated Gene That Mediates Metastatic Migration and Invasion in Breast Cancer[J]. Cancer Res, 2016, 76(17): 4994-5005. DOI:10.1158/0008-5472.CAN-15-2322.
[23]Sun R, Jiang B, Qi H, et al. SOX4 contributes to the progression of cervical cancer and the resistance to the chemotherapeutic drug through ABCG2[J]. Cell Death Dis, 2015, 6: e1990. DOI:10.1038/cddis.2015.290.
[24]Foronda M, Morgado-Palacin L, G mez-L pez G, et al. Profiling of Sox4-dependent transcriptome in skin links tumour suppression and adult stem cell activation[J]. Genomics Data, 2015, 6: 21-24. DOI:10.1016/j.gdata.2015.07.030.
[25]Shen H, Blijlevens M, Yang N, et al. Sox4 Expression Confers Bladder Cancer Stem Cell Properties and Predicts for Poor Patient Outcome[J]. Int J Biol Sci, 2015, 11(12): 1363-1375. DOI:10.7150/ijbs.13240.

相似文献/References:

[1]李明,孙守兵,周越,等.去甲肾上腺素诱导人巨噬细胞MMP-9的表达及机制[J].第三军医大学学报,2012,34(17):1758.
 Li Ming,Sun Shoubing,Zhou Yue,et al.Norepinephrine induces expression of matrix metalloproteinase-9 in human macrophages and its mechanisms[J].J Third Mil Med Univ,2012,34(09):1758.
[2]王艺明,杨宗城.去甲肾上腺素对严重烧伤大鼠脑水肿的影响[J].第三军医大学学报,2005,27(18):1833.
[3]韩京,冉新泽,艾国平,等.去甲肾上腺素促进骨髓间充质干细胞增殖的研究[J].第三军医大学学报,2009,31(23):2295.
 HAN Jing,RAN Xin-ze,AI Guo-ping,et al.Norepinephrine improves bone marrow mesenchymal stem cells proliferation through AR/PKC-dependent signaling[J].J Third Mil Med Univ,2009,31(09):2295.
[4]周建云,周琳琳,严军,等.去甲肾上腺素对脂多糖诱导的巨噬细胞活化的影响[J].第三军医大学学报,2009,31(13):1278.
 ZHOU Jian-yun,ZHOU Lin-lin,YAN Jun,et al.Effects of norepinephrine on the activation of LPS-induced macrophages[J].J Third Mil Med Univ,2009,31(09):1278.
[5]张恒,王培勇,刘健,等.BAPTA对去甲肾上腺素刺激的大鼠心肌细胞蛋白合成及c-fos和β-MHC表达的影响[J].第三军医大学学报,2005,27(15):1534.
[6]游波,许月明,陈虎平,等.多巴胺联合去甲肾上腺素对危重患者血流动力学的稳定作用[J].第三军医大学学报,2011,33(21):2323.
[7]陈吉,黄岚,吴强,等.去甲肾上腺素刺激乳鼠心肌细胞内活性氧产生受体途径的研究[J].第三军医大学学报,2004,26(08):0.[doi:10.16016/j.1000-5404.2004.08.015 ]
 CHEN Ji,HUANG Lan,WU Qiang.[J].J Third Mil Med Univ,2004,26(09):0.[doi:10.16016/j.1000-5404.2004.08.015 ]
[8]刘晓红,魏振宇,高原,等.大鼠心室肌α1-肾上腺素能受体介导的c-fos、c-myc表达[J].第三军医大学学报,2004,26(13):0.[doi:10.16016/j.1000-5404.2004.13.010 ]
 LIU Xiao-hong,WEI Zhen-yu,GAO Yuan.[J].J Third Mil Med Univ,2004,26(09):0.[doi:10.16016/j.1000-5404.2004.13.010 ]
[9]陈康宁,瞿伟,覃园园,等.焦虑抑郁障碍患者ET的变化[J].第三军医大学学报,2004,26(16):0.[doi:10.16016/j.1000-5404.2004.16.002 ]
[10]周元国,王正国,朱佩芳,等.G蛋白在心血管功能调节及急性肺损伤中的作用研究[J].第三军医大学学报,1997,19(02):0.[doi:10.16016/j.1000-5404.1997.02.024 ]

更新日期/Last Update: 2017-05-04