|本期目录/Table of Contents|

姜黄素调控Notch信号通路对肺癌干细胞增殖及凋亡的影响

《现代肿瘤医学》[ISSN:1672-4992/CN:61-1415/R]

期数:
2018年20期
页码:
3199-3204
栏目:
论著（基础研究）
出版日期:
2018-09-08

文章信息/Info

Title:
Effect of curcumin on lung cancer stem cells via Notch signaling pathway
作者:
杨秦梅1; 崔青荣1; 李 彬2; 李 宁3; 周庆伟1
1.河南中医药大学第一附属医院呼吸三区；2.呼吸二区；3.呼吸内科，河南 郑州 450000
Author(s):
Yang Qinmei1; Cui Qingrong1; Li Bin2; Li Ning3; Zhou Qingwei1
1.Department of Respiration Ⅲ;2.Department of RespirationⅡ;3.Department of Respiratory Medicine,The First Affiliated Hospital of Henan University of TCM,Henan Zhengzhou 450000,China.
关键词:
姜黄素; Notch信号通路; 干细胞; 增殖; 凋亡
Keywords:
curcumin; Notch signaling pathway; stem cells; proliferation; apoptosis
分类号:
R734.2
DOI:
10.3969/j.issn.1672-4992.2018.20.007
文献标识码:
A
摘要:
目的：研究姜黄素对肺癌干细胞增殖及凋亡的影响。方法:利用免疫磁珠标记肺癌表面标记物乙醛脱氢酶1(ALDH1)，从肺癌A549细胞系中分离肺癌干细胞；MTT实验检测姜黄素对肺癌干细胞增殖的影响；流式细胞仪检测姜黄素对肺癌干细胞凋亡的影响；Western blot检测Notch1和Hes1蛋白的表达情况；抑制剂γ-分泌酶抑制Notch信号通路研究对肺癌干细胞增殖及凋亡的影响。结果:利用免疫磁珠分选法分选出肺癌细胞系A549中ALDH1+肺癌干细胞。MTT检测结果显示，姜黄素能够呈浓度依赖性的抑制肺癌干细胞的增殖；经姜黄素处理后的肺癌干细胞，与对照组相比，凋亡率明显升高，Notch1和Hes1蛋白的表达明显下降。经γ-分泌酶抑制剂处理肺癌干细胞后，实验结果显示，γ-分泌酶抑制剂通过下调Notch1和Hes1蛋白的表达调控Notch信号通路抑制肺癌干细胞的增殖，诱导其凋亡。结论:姜黄素抑制肺癌干细胞的增殖，诱导其凋亡与Notch信号通路有关。
Abstract:
Objective:To explore the effect of curcumin on the proliferation and apoptosis of lung cancer stem cell.Methods:The surface markers（ALDH1) and lung cancer stem cells by using the immune magnetic beads were isolated from lung cancer A549 cell line.The effect of curcumin on the proliferation of lung cancer stem cell was determined by MTT test.Flow cytometry instrument was used to detect the influence curcumin on the apoptosis of lung cancer stem cell.Western blot was used to detect the expression levels of Notch1 and Hes1.Gamma secretase inhibitors inhibit the Notch signaling pathway in lung cancer stem cell proliferation and apoptosis.Research the effects of Gamma secretase inhibitors on the proliferation and apoptosis of lung cancer stem cell by inhibitting the Notch signaling pathway.Results:The ALDH1+ lung cancer stem cells were sorted out from the lung cancer A549 cell line by using immune magnetic bead separation method.The results of MTT test show that the curcumin can inhibit the proliferation of lung cancer stem cell by concentration dependence.After the treatment of curcumin in lung cancer stem cells,the apoptosis rate increased significantly,and the protein expression levels of Notch1 and Hes1 decreased obviously,compared with control group.After the treatment of gamma secretase inhibitors in lung cancer stem cells,the experimental results showed that gamma secretase inhibitors by cutting Notch signaling pathway regulated the protein expression levels of Notch1 and Hes1 and inhibited the proliferation of lung cancer stem cell and induced its apoptosis.Conclusion:The results suggest that curcumin can inhibit the proliferation of lung cancer stem cell and induce its apoptosis associated with Notch signal pathway.

参考文献/References

[1]Sheehan DF,Criss SD,Gazelle GS,et al.Evaluating lung cancer screening in China:Implications for eligibility criteria design from a microsimulation modeling approach［J］.PLoS One,2017,12(3):e0173119.
[2]Malhotra J,Malvezzi M,Negri E,et al.Risk factors for lung cancer worldwide［J］.European Respiratory Journal,2016,48(3):889.
[3]Zhang H,Zhang S.Present situation of lung cancer screening methods［J］.Chinese Journal of Lung Cancer,2016,19(10):715-720.
[4]Jin FG.Analysis of the status of early lung cancer screening in China［J］.Clinical Decision Study,2017,38（1B):15-18.［金发光.我国肺癌早期筛查现状分析［J］.临床决策研究,2017,38(1B):15-18.］
[5]Dong YL,Gao HM,Chen WL,et al.Research progress in early diagnosis of lung cancer［J］.Chinese Disaster Relief Medicine,2017,5（1):55-58.［董友玲,高红梅,陈文丽,等.肺癌早期诊断方法的研究进展［J］.中华灾害救援医学,2017,5(1):55-58.］
[6]Xia B,Jiang H,Wang LM,et al.Clinical research progress of lung cancer for 30 years［J］.Journal of Practical Cancer,2016,31（4):296-300.［夏冰,江洪,王利民,等.肺癌30年临床研究进展［J］.实用肿瘤杂志,2016,31(4):296-300.］
[7]Liu ZL,Xiao GM,Chen YJ,et al.The development of lung cancer stem cells and lung cancer［J］.Research on Organizational Engineering in China,2014,18（28):4568-4572.［刘哲亮,肖高明,陈跃军,等.肺癌干细胞与肺癌的发生［J］.中国组织工程研究,2014,18(28):4568-4572.］
[8]Yang D,Zhang PT.Progress in the research of lung cancer stem cells［J］.Chinese Tumor,2015,24（7):574-580.［杨栋,张培彤.肺癌干细胞研究进展［J］.中国肿瘤,2015,24(7):574-580.］
[9]Zhang K,Jiang C,Wang P.Human lung cancer stem cell［J］.Chemistry of Life,2013,33(4):433-437.
[10]Templeton AK,Miyamoto S,Babu A,et al.Cancer stem cells:Progress and challenges in lung cancer［J］.Stem Cell Investigation,2014,1(9):9.
[11]Suresh R,Ali S,Ahmad A,et al.The role of cancer stem cells in recurrent and drug-resistant lung cancer［J］.Lung Cancer and Personalized Medicine,2016,890(3):57-74.
[12]Roudi R,Korourian A,Shariftabrizi A,et al.Differential expression of cancer stem cell markers ALDH1 and CD133 in various lung cancer subtypes［J］.Cancer Investigation,2015,33(7):294.
[13]Liu ZL,Xiao GM,Chen YJ,et al.Research status of stem cell markers for lung cancer［J］.Chinese Journal of Thoracic and Cardiovascular Surgery,2014,21（4):537-541.［刘哲亮,肖高明,陈跃军,等.肺癌干细胞标志物的研究现状［J］.中国胸心血管外科临床杂志,2014,21(4):537-541.］
[14]Hu TH,Xu XX.Progress in the research of stem cell markers for lung cancer［J］.The Electronic Edition of the Chinese Journal of Lung Disease,2015,8（5):82-85.［胡腾惠,徐兴祥.肺癌干细胞标志物的研究进展［J］.中华肺部疾病杂志(电子版),2015,8(5):82-85.］
[15]Sun HY,Yang M,Zheng MJ,et al.Expression of CD133 and ALDH1 in non-small cell lung cancer and its clinical significance［J］.Journal of Clinical and Experimental Pathology,2012,28（7):813-815.［孙慧元,杨敏,郑茂金,等.非小细胞肺癌组织中CD133和ALDH1的表达及其临床意义［J］.临床与实验病理学杂志,2012,28(7):813-815.］
[16]Zhuo Y,Liang D.Study of ALDH1 as a functional marker of lung cancer stem cells［J］.Modern Integrated Traditional Chinese and Western Medicine Magazine,2015,24（33):3652-3654.［卓越,梁冬.ALDH1作为肺癌干细胞功能标志物的研究［J］.现代中西医结合杂志,2015,24(33):3652-3654.］
[17]Liang HX,Zhong H,Luo Y,et al.Expression and significance of cancer stem cell，arkers CD133,CD44,SOX2,OCT4 and ALDH1 in non-small cell lung cancer［J］.Practical Journal of Cancer,2013,40(12):472-475.
[18]Liu H,Guo JM,Wang HY,et al.Research progress of curcumin pharmacological action and mechanism［J］.China Journal of Modern Medicine,2012,22(6):48-51.
[19]Wang YZ,Zhang N,University CM,et al.Research progress of the antitumor effect of curcumin［J］.Journal of Baoji University of Arts & Sciences,2015,35(1):41-47.
[20]Li ZC,Zhang LM,Wang HB,et al.Curcumin inhibits lung cancer progression and metastasis through induction of FOXO1［J］.Tumor Biology,2014,35(1):111-116.
[21]Chen S,Dechuan LI.Induction of apoptosis by curcumin in human lung cancer cell line［J］.Medical Journal of Wuhan University,2012,33(4):507-510.
[22]Zhao YR,Zhang LF,Liu T.Effect of curcumin on the proliferation and invasion of human lung cancer stem cells after up regulation of Caspase-3 and p53［J］.Chinese Clinical Medicine,2013,20（3):259-262.［赵雅瑞,张立凡,刘特.姜黄素上调Caspase-3和p53表达后对人肺癌干细胞增殖与侵袭的影响［J］.中国临床医学,2013,20(3):259-262.］
[23]Cheng JH,Liu S,Han Z,et al.Curcumin promotes proliferation and migration of neural stem cells in cerebral ischemic rats by regulating Notch signaling［J］.Chinese Journal of Pathophysiology,2013,29(5):878-882.
[24]Zhang QJ,Liu ML,Zhao Y,et al.The scientific significance of tumor stem cell theory in medical research［J］.Gansu Science and Technology,2015,31（19):127-129.［张秋菊,刘茗露,赵翊,等.肿瘤干细胞理论在医学研究中的科学意义［J］.甘肃科技,2015,31(19):127-129.］
[25]She J,Yang P,Hong Q,et al.Lung cancer in China:Challenges and interventions［J］.Chest Journal,2013,143(4):1117-1126.
[26]Zhao Runan,Ruan Yonghua,Ma Liju.Progress in the research of lung cancer stem cells［J］.Modern Oncology,2015,23（11):1620-1624.［赵汝楠,阮永华,马丽菊.肺癌干细胞的研究进展［J］.现代肿瘤医学,2015,23(11):1620-1624.］
[27]Jiang AG,Lu HY,Zhang DG,et al.Short hairpin RNA targeting AKT1 and PI3K/p85 suppresses the proliferation and self-renewal of lung cancer stem cells［J］.Molecular Medicine Reports,2015,12(1):363.
[28]Jiang HL,Jiang LM,Han WD.Wnt/β-catenin signaling pathway in lung cancer stem cells is a potential target for the development of novel anticancer drugs［J］.Official Journal of the Balkan Union of Oncology,2015,20(4):1094.
[29]Huang CP,Tsai MF,Chang TH,et al.ALDH-positive lung cancer stem cells confer resistance to epidermal growth factor receptor tyrosine kinase inhibitors［J］.Cancer Letters,2013,328(1):144-151.
[30]Tirino V.Cancer stem cells in solid tumors:An overview and new approaches for their isolation and characterization［J］.The Faseb Journal,2013,27(1):13-24.
[31]Xia XY,Zheng XL,Ding N,et al.Research Progress on the culture,identification and application of lung cancer stem cells［J］.Canceration?Distortion?Mutation,2016,28（4):321-324.［夏学阳,郑鑫林,丁楠,等.肺癌干细胞培养、鉴定及其应用的研究进展［J］.癌变?畸变?突变,2016,28(4):321-324.］
[32]Lanying Gou,Yilong Wu.Signaling pathway of cancer stem cells in small cell lung cancer［J］.Chinese Clinical Oncology,2013,18(1):89-92.
[33]Kuang LS.Progress in the study of Wnt and Notch signaling pathways in the regulation of lung cancer stem cells［J］.Medical Review,2013,19（2):268-271.［况里杉.Wnt和Notch信号通路在肺癌干细胞调控中的研究进展［J］.医学综述,2013,19(2):268-271.］
[34]Tan AH,Chen SY.Research progress on antitumor effect of curcumin［J］.The Contemporary Medical Journal,2015,13（7):134-135.［谭爱华,陈诗雅.浅论对姜黄素抗肿瘤作用的研究进展［J］.当代医药论丛,2015,13(7):134-135.］
[35]He DL.Curcumin effect on proliferation and apoptosis of gastric cancer stem cells via ATK/FoxM1 signaling pathway［J］.Chinese Journal of Tissue Engineering Research,2016,20（32):4731-4737.［贺东黎.姜黄素通过ATK/FoxM1信号通路调控胃癌干细胞增殖及凋亡［J］.中国组织工程研究,2016,20(32):4731-4737.］
[36]Shu XL,He XD,Li Q,et al.The influence of radiotherapy sensitivity of curcumin on CD133+ tumor stem cell like cell populations in rectal carcinoma［J］.Chinese Journal of Gerontology,2015,35（4):1013-1015.［舒小镭,何笑冬,李倩,等.姜黄素对直肠癌CD133+肿瘤干细胞样细胞群放疗敏感性的影响［J］.中国老年学,2015,35(4):1013-1015.］
[37]Chen F,Wang HX,Xiang X,et al.In vitro study of the effect of curcumin on the expression of Wnt/ beta-catenin signaling pathway in neural stem cells in vitro［J］.Journal of Third Military Medical University,2014,36（8):764-768.［陈飞,王皓香,向鑫,等.姜黄素对神经干细胞Wnt/β-catenin信号通路表达影响的离体研究［J］.第三军医大学学报,2014,36(8):764-768.］
[38]Liu JT.Expression and role of Notch signaling pathway in CD133 positive lung cancer cells［D］.Wuhan:Wuhan University,2014:1-76.［刘军韬.Notch信号通路在CD133阳性肺癌细胞中的表达及其作用的研究［D］.武汉:武汉大学,2014:1-76.］

备注/Memo

备注/Memo:
National Natural Science Foundation of China(No.81501991）；国家自然科学基金青年项目（编号：81501991）;河南省高等学校重点科研项目（编号：18A360010）
更新日期/Last Update: 2018-08-31