您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报(医学版) ›› 2017, Vol. 55 ›› Issue (3): 32-37.doi: 10.6040/j.issn.1671-7554.0.2016.458

• 基础医学 • 上一篇    下一篇

去甲斑蝥素对骨髓瘤U266细胞Notch信号通路表达的影响

郭贺贺1,孙志强2,3,刘艳娟1,刘奕晨1,李广1,郑方2,3   

  1. 1. 贵州医科大学研究生院, 贵州 贵阳 550004;2. 贵州医科大学附属白云医院血液科, 贵州 贵阳 550014;3. 贵州医科大学附属医院血液科, 贵州 贵阳 550004
  • 收稿日期:2016-04-25 出版日期:2017-03-10 发布日期:2017-03-10
  • 通讯作者: 郑方. E-mail:1179556708@qq.com E-mail:1179556708@qq.com
  • 基金资助:
    贵州省科学技术基金项目(TJ2014-4);贵阳市白云区科技基金项目(白科合同2014年度6号)

Norcantharidin influences the expression of Notch signal pathway in multiple myeloma U226 cells

GUO Hehe1, SUN Zhiqiang2,3, LIU Yanjuan1, LIU Yichen1, LI Guang1, ZHENG Fang2,3   

  1. 1. Graduate School, Guizhou Medical University, Guiyang 550004, Guizhou, China;
    2. Department of Hematology, Baiyun Affiliated Hospital of Guizhou Medical University, Guiyang 550014, Guizhou, China;
    3. Department of Hematology, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China
  • Received:2016-04-25 Online:2017-03-10 Published:2017-03-10

摘要: 目的 探讨去甲斑蝥素(NCTD)对人多发性骨髓瘤U266细胞Notch信号通路表达的影响。 方法 体外培养骨髓瘤U266细胞,不同浓度(10、20、40、80 μmol/L)NCTD与U266细胞共同孵育后,采用CCK-8法检测细胞增殖抑制率;采用流式细胞术检测细胞凋亡率;采用qRT-PCR、Western blotting法检测细胞Notch2、Hes1、CyclinD1和P21基因蛋白的表达。 结果 20、40、80 μmol/L NCTD能抑制U266细胞增殖,诱导细胞凋亡,其抑制效应具有时间和浓度依赖性;NCTD可上调瘤细胞中Notch2和P21基因蛋白的表达,同时降低Hes1和CyclinD1表达。 结论 NCTD能够抑制骨髓瘤细胞增殖,且能诱导细胞凋亡;细胞凋亡的发生可能与Notch 信号通路中Notch2、P21表达上调,CyclinD1和Hes1的表达下调有关。

关键词: 多发性骨髓瘤, U266细胞, 去甲斑蝥素, Notch信号通路, 细胞凋亡

Abstract: Objective To investigate the effects of norcantharidin(NCTD)on the expression of Notch signal pathway in multiple myeloma U226 cells. Methods U226 cells were co-cultured with NCTD at various concentrations in vitro. The proliferation inhibition was measured with CCK-8 test. The cell apoptosis rate was analyzed with flow cytometry. The mRNA and protein expressions of Notch2, Hes1, CyclinD1 and P21 in U266 cells were detected with qRT-PCR and Western blotting. Results NCTD could inhibit the proliferation of U266 cells and induce the apoptosis of cells in a time- and concentration-dependent manner. The mRNA and protein expressions(Notch2, P21)elevated with increased concentration of NCTD, while the expression of Hes1 and CyclinD1 decreased. Conclusion NCTD can inhibit the proliferation and induce the apoptosis of U266 cells, which may be related to the up-regulation of Notch2 and P21, and the down-regulation of CyclinD1 and Hes1.

Key words: Multiple myeloma, Notch signal pathway, Norcantharidin, U266 cells, Apoptosis

中图分类号: 

  • R932
[1] Colombo M, Mirandola L, Platonova N, et al. Notch-directed microenvironment reprogramming in myeloma:a single path to multiple outcomes[J]. Leukemia, 2013, 27(5):1009-1018.
[2] Aster JC, Blacklow SC, Pear WS. Notch signaling in T-cell lymphoblastic leukaemia/lymphoma and other haematological malignancies[J]. J Pathol, 2011, 223(2): 262-273.
[3] Lee JY, Song SY, Park JY. Notch pathway activation is associated with pancreatic cancer treatment failure[J]. Pancreatology, 2014, 14(1):48 -53.
[4] 张金巧, 戴晓丽,蒙艳凤, 等. 去甲斑蝥素对人多发性骨髓瘤细胞株U266生长调控的影响及其机制的研究[J]. 河北医科大学学报, 2010, 31(8): 896-897. ZHANG Jinqiao, DAI Xiaoli, MENG Yanfeng, et al. Effect of Norcantharidin of on the growth control of human myeloma cell line U266 and its mechanism[J]. Journal of Hebei Medical University, 2010, 31(8):896-897.
[5] Xiong X, Wu M, Zhang H, et al. Atg5 siRNA inhibits autophagy and enhances norcantharidin-induced apoptosis in hepatocellular carcinoma[J]. Int J Oncol, 2015, 47(4):1321-1328.
[6] Xie J, Zhang Y, Hu X, et al. Norcantharidin inhibits Wnt signal pathway via promoter demethylation of WIF-1 in human non-small cell lung cancer[J]. Med Oncol, 2015, 32(5):145.
[7] Zheng LC, Yang MD, Kuo CL, et al. Norcantharidin-induced apoptosis of AGS human gastric cancer cells through reactive oxygen species production, and caspase- and mitochondria-dependent signaling pathways[J]. Anticancer Res, 2016, 36(11): 6031-6042.
[8] Guo D, Li C, Teng Q, et al. Notch1 overexpression promotes cell growth and tumor angiogenesis in myeloma[J]. Neoplasma, 2013, 60(1): 33-40.
[9] 卢燕燕, 肖翠容, 陈华英, 等. 阿霉素诱导的骨髓瘤细胞化疗耐药的分子机制分析[J]. 中国实验血液学杂志, 2014, 22(5): 1336-1340. LU Yanyan, XIAO Cuirong, CHEN Huaying, et al. Molecular mechanism of Doxorubicin resistance in multiple myeloma cell line[J]. Journal of Experimental Hematology, 2014, 22(5): 1336-1340.
[10] Xu D, Hu J, De Bruyne E, et al. Dll1/Notch activation contributes to bortezomib resistance by upregulating CYP1A1 in multiple myeloma[J]. Biochem Biophys Res Commun, 2012, 428(4):518-524.
[11] Li X, He X, Tian W, et al. Short hairpin RNA targeting Notch2 inhibits U87 human glioma cell proliferation by inducing cell cycle arrest and apoptosis in vitro and in vivo[J]. Mol Med Rep, 2014, 10(6):2843-2850.
[12] 杨春秀, 陈建斌, 张树君, 等. Notch2胞内段基因过表达对K562细胞增殖的影响及其机制[J]. 中国生物制品学杂志, 2011, 24(11):1278-1289. YANG Chunxiu, CHEN Jianbin, ZHANG Shujun, et al. Effect of Overexpression of Intracellular Domain of Notch2 Gene on Prolifera-tion of K562 Cells and Relevant Mechanism[J]. Chin J Biologicals, 2011, 24(11):1278-1289.
[13] Ramakrishnan V, Ansell S, Haug J, et al. MRK003, a γ-secretase inhibitor exhibits promising in vitro pre-clinical activity in multiple myeloma and non-Hodgkin's lymphoma[J]. Leukemia, 2012, 26(2):340-348.
[14] Schwarzer R, Nicke N, Godau J, et al. Notch pathway inhibition controls myeloma bone disease in the murine MOPC315.BM model[J]. Blood Cancer Journal, 2014, 4(6):217.
[15] Yao J, Zheng K, Li C, et al. Interference of Notch1 inhibits the growth of glioma cancer cells by inducing cell autophagy and down-regulation of Notch1-Hes-1 signaling pathway[J]. Med Oncol, 2015, 32(6):174-181.
[16] Zhang W, Nie Y, Chong L, et al. PI3K and Notch signal pathways coordinately regulate the activation and proliferation of T lymphocytes in asthma[J]. Life Sci, 2013, 92(17-19):890-895.
[17] Gopalakrishnan N, Saravanakumar M, Madankumar P, et al. Colocalization of β-catenin with Notch intracellular domain in colon cancer: a possible role of Notch1 signaling in activation of CyclinD1-mediated cell proliferation[J]. Mol Cell Biochem, 2014, 396(1-2):281-293.
[18] Cornils H, Kohler RS, Hergovich A, et al. Human NDR kinases control G1/S Cell Cycle transition by directly regulating p21 stability[J]. Mol Cell Biol, 2011, 31(7): 1382-1395.
[19] Ke X, Zhao Y, Lu X, et al. TQ inhibits hepatocellular carcinoma growth in vitro and in vivo via repression of Notch signaling[J]. Oncotarget, 2014, 6(32): 32610-32612.
[20] Cialfi S, Palermo R, Manca S, et al. Loss of Notch1-dependent p21(Waf1/Cip1)expression influences the Notch1 outcome in tumorigenesis[J]. Cell Cycle, 2014, 13(13):2046-2055.
[21] 李斑斑. 乏氧与 Notch1对人多发性骨髓瘤细胞增殖和凋亡的影响[D]. 泰安: 泰山医学院, 2014: 2-6.
[1] 鹿向东 杨伟 徐广明 曲元明. 脑膜瘤中PPAR-γ的表达及曲格列酮对脑膜瘤培养细胞生长的影响[J]. 山东大学学报(医学版), 2209, 47(6): 65-.
[2] 李红志,刘静,宋岩,迟令懿,刘玉光. 利拉鲁肽对脊髓损伤修复作用的探讨[J]. 山东大学学报(医学版), 2016, 54(4): 1-5.
[3] 郝风芹,李娜. 洋葱总黄酮对大鼠糖尿病视网膜神经节细胞的神经保护作用[J]. 山东大学学报(医学版), 2016, 54(1): 7-10.
[4] 程翔宇, 邢锐, 邢召全, 郭兆新, 郭晓宇, 苏静, 孟力维, 刘照旭. 氯化两面针碱对前列腺癌细胞PC-3增殖与凋亡的影响[J]. 山东大学学报(医学版), 2015, 53(9): 13-18.
[5] 于淑萍, 李雪飞, 王丹, 王玉坤. PDCD4和survivin在尖锐湿疣、鲍恩样丘疹病、Bowen病及鳞状细胞癌皮损中的表达[J]. 山东大学学报(医学版), 2015, 53(7): 82-86.
[6] 周静, 常晓天, 周婷, 崔莹莹, 张蓓, 荣风年. 沉默PADI4基因对卵巢癌细胞系OVCAR3的作用[J]. 山东大学学报(医学版), 2015, 53(6): 48-53.
[7] 刘琼, 蒲业迪, 代广霞, 马家乐, 杨建霞, 李丽珍, 李颢, 王鲁群. 硼替佐米耐药多发性骨髓瘤细胞基因表达谱分析[J]. 山东大学学报(医学版), 2015, 53(6): 33-38.
[8] 于昕, 刘晓静, 刘向群. 黄芩苷抑制ox-LDL诱导内皮细胞凋亡的作用[J]. 山东大学学报(医学版), 2015, 53(5): 5-9.
[9] 涂云华, 康颖倩, 周英, 叶振源, 薛月萃, 邓仁远, 王梅竹, 陈兰, 曹煜. 姜黄挥发油对THP-1细胞增殖及凋亡的影响[J]. 山东大学学报(医学版), 2015, 53(5): 46-51.
[10] 游洁冰, 孙忠文, 杜鹃, 胥文娟, 王雅琳, 李帅, 朱梅佳. 罗格列酮、胰岛素对Ⅱ型糖尿病大鼠脑内TIPE2的表达和细胞凋亡的影响[J]. 山东大学学报(医学版), 2015, 53(4): 43-48.
[11] 杨璐, 刘延国, 李际盛, 王秀问. 蟾毒灵对非小细胞肺癌顺铂化疗的增敏作用及机制[J]. 山东大学学报(医学版), 2015, 53(3): 6-11.
[12] 李红霞, 董蕾, 姜炅, 王新阳. 酪酪肽对胰腺癌Miapaca-2细胞凋亡的影响[J]. 山东大学学报(医学版), 2015, 53(12): 7-11.
[13] 张伟, 周勇, 牛俊婕, 徐英, 侯华英, 姜玉华. 抗癫痫药丙戊酸钠对大鼠正常脑组织的放射保护作用[J]. 山东大学学报(医学版), 2015, 53(10): 11-15.
[14] 付海燕, 胡占升, 杜红阳, 李潮, 包翠芬. 地黄多糖对过表达Notch1(NICD)大鼠骨髓间充质干细胞诱导分化及增殖的影响[J]. 山东大学学报(医学版), 2015, 53(1): 34-40.
[15] 彭静, 李卉, 杜玮. 皮下注射硼替佐米的护理体会[J]. 山东大学学报(医学版), 2014, 52(Z1): 180-181.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!