多不饱和脂肪酸不同组分抑制肺腺癌干细胞作用研究*

南京大学学报(自然科学版) ›› 2013, Vol. 49 ›› Issue (1): 116–122.

多不饱和脂肪酸不同组分抑制肺腺癌干细胞作用研究*

胡振东1·2，尹荣2，武雅琴2，张治2，李明2，贾辉2，许林2，李宁1**

出版日期:2015-09-18 发布日期:2015-09-18
作者简介:(1.南京大学医学院，南京，210093;2.江苏省肿瘤医院胸外科，南京，210009)

The study of polyunsaturated fatty acids components inhibiting
lung adenocarcinoma stem cells

Hu Zhen Donh 1’2 ,Yin Rong2 ,Wu Ya-Qin2，Zhang Zhi2,Li Ming2，Jia Hui2，Xu Lin2，Li Ning1

Online:2015-09-18 Published:2015-09-18
About author: (1. Medical School , Nanjing University, Nanjing, 210093 , China;
2.Thoracic Department,Jiangsu Cancer Hospital,Nanjing,210009,China)

摘要/Abstract

摘要： 比较多不饱和脂肪酸(PUFA)各有效成分抑制肺腺癌干细胞增殖及迁移能力，筛选出最强组分，并探讨其量效关系.对肺腺癌细胞株A549及SPC-A-1进行无血清培养，待肿瘤干细胞(CSC)微球形成后，每口分别加入50 umol/L的α-麻酸((LA)、二十碳五烯酸(EPA)、二十二碳六烯酸(DHA),c9,t11一共轭亚油酸(c9, t11-CLA)和tl0,cl2一共轭亚油酸(t1 0, c1 2-CLA)，连续3d.分别行干细胞微球形成观察、干细胞微球定量分析，筛选出最强组分.加入不同浓度最强组分进行侵袭试验.干细胞微球定量分析显示:除 LA外，EPA,DHA,c9,t11-CLA和t10, c12-CLA都可不同程度地抑制A549及SPC-A-1干细胞微球的形成.在两种细胞株中，与EPA及DHA组相比，同等浓度CLA组平均干细胞微球个数及单个微球干细胞密度均显著卜降，表明两种CLA为抑制作用最强组分.选取最强组分CLA行侵袭试验，c9 , t11-CLA, t10 , c12-CLA均能不同程度地抑制肺癌干细胞的迁移及浸润能力，随着浓度的增加，抑制作用增加，两者混合物的抑制作用最强.结果说明，PUFA组分EPA,DHA,c9,t11-CLA和t10, c12-CLA对A549及SPC-A-1干细胞微球都有不同程度的抑制作用，其中c9, t11-CLA和t10, c12-CLA为最强组分.c9 , t11-CLA和t10, c12-CLA体外试验能够不同程度的抑制肺腺癌干细胞的浸润和迁移能力，并具有剂量依赖性.

Abstract: The purpose of the study is to compare the effect of each polyunsaturated fatty acids(PUFA)active ingredient inhibiting the proliferation and invasion capacity of lung adenocarcinoma stem cclls,and to screen the strongest component out and explore its dose-effect relationship. A549 and SPC-A-1 were cultivated under serum-free condition,and after the for- mation of cancer stem cells(CSC) microspheroids, 50 umol/L LA, EPA, DHA, c9，t11-CLA and t10，c12-CLA were added respectively every day for three days.The most potent components were selected by observing the formation of stem cell mi crosphoids and quantitative analysis of stem cell microsphoids.The most potent components in different concentrations were added to carry out the tumour invasion assay.The quantitative analysis results of stem cell microspheroids showed that EPA,DHA,c9,t11-CLA and t10,c12-CLA can inhibit the formation of A549 and SPC-A-1 stem cell microspheroids in var ying degrees except LA. In these two cell lines,the average number of stem cell microspheroids and the density of single mi crospheroid stem cell wrere significantly decreased in the groups with same concentration CLA, compared with EPA and DHA groups,which showed that two CLA wrere the components having strongest inhibiting effects.The strongest compo nent,CLA,was selected to carry out the tumour invasion assay,and the results showed that; both c9,t11-CLA and tl0,cl2- CLA could inhihit the ahilitics of invasion of lung cancer stem cell in varying degrees. With increase of concentration, the effects of inhibition were improved correspondingly, and the mixture of two CLA components had strongest inhibiting effects. PUFA components EPA,DHA,c9,t11-CLA and t10,c12-CLA all had inhihitivc effects on A549 and SP(-A-1 stem cell microspheroids in varying degrees, and c9，t11-CLA and t10，c12-CLA are strongest components.The in vitro test showed that c9,t11-CLA and t10,c12-CLA could inhibit the abilities of invasion of lung adenocarcinoma stem cells in var ying degrees,have dose dependence

胡振东1·2，尹荣2，武雅琴2，张治2，李明2，贾辉2，许林2，李宁1**
. 多不饱和脂肪酸不同组分抑制肺腺癌干细胞作用研究*[J]. 南京大学学报(自然科学版), 2013, 49(1): 116–122.

Hu Zhen Donh 1’2 ,Yin Rong2 ,Wu Ya-Qin2，Zhang Zhi2,Li Ming2，Jia Hui2，Xu Lin2，Li Ning1
. The study of polyunsaturated fatty acids components inhibiting
lung adenocarcinoma stem cells[J]. Journal of Nanjing University(Natural Sciences), 2013, 49(1): 116–122.

参考文献

[1] Courtney E D,Maztthews S,Finlayson C,et al. Eicos-apentacnoic acid(EPA)reduces crypt cell proliferation and increases apoptosis in normal colonic mucosa in subjects with a history of colorectal adenomas. Intci-national Journal of Colorectal Disease, 2007 (22):765-776. [2]Fradet V,Cheng I,Cascy G,et al. Dietary omega-3 fatty acids, cyclooxygenase-2 genetic variation, and aggressive prostate cancer risk. Clinical Cancer Re search,2009(15):2559一2566. [3]Thiebaut A C, Chajes V, Gerber M, et al. Dietary intakes of omegx6 and omega-3 polyunsaturated fatty acids and the risk of breast cancer.International Journal of Cancer, 2009(124):924~931. [4]Wolk A, Larsson S C, Johansson J E, et al. Long-term fatty fish consumption and renal cell carcinoma incidence in women.The Journal of the American Medical Association,2006(296):1371一1376. [5]Hardman W F.(n一3) fatty acids and cancer therapy.Journal of Nutrition, 2004，134(12 Suppl):3427S一3430S. [6]Gleissman H,Johnsen J I，Kogner P. Omcga-3 fatty acids in cancer,the protectors of good and the killers of evil? Experimental Cell Research, 2010，316(8):1365一1373. [7]Elaine H W. (n -3)Fatty acids and cancer therapy.Journal oI Nutrition,2004，134:3427S-3430S. [8]Dela "Iorre A,Debiton E,Durand D,et al. Conjugated linolcic acid isomers and their conjugated derivatives inhibit growth of human cancer cell lines. Anticancer Research,2005,25(6B) ,3943一3949. [9]Hubbard N E,Lim D,Summers L,et al. Reduction of murine mammary tumor metastasis by conjugated lin- oleic acid. Cancer Letters,2000, 150(01):93一100. [10]Erickson K L, Hubbard N E. Fatty acids and breast cancer; the role of stem cells. Prostaglandins Leukot Essent Fatty Acids,2010,82(4一6);237一241. [11]Bhattacharya A,Banu J,Rahman M,et al. Biological effects of conjugated linolcic acids in health and dis ease. Journal of Nutritional Biochemistry, 2006，17:789一810. [12]Beppu F, Hosokawa M, Tanaka L, et al. Potent in hibitory effect of trans9，transll isomer of conjugated linolcic acid on the growth of human colon cancer cells. Journal of Nutritional Biochemistry, 2006，17;830一836. [13]Palombo J D, Ganguly A, Bistrian B R, et al. The antiproliferative effects of biologically active isomers of conjugated linolcic acid on human colorectal and prostatic cancer cells. Cancer Letters, 2002，177:163 ~172. [14]Kucia M, Reca R，Mickus K, et al. Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms; pivotal role of the SDF-1-CXCR4 axis. Stem Cells, 2005，23(7):879-894. [15]Singh S K, Hawkins C,Clarke l D,et al. Identification of human brain tumour initiating cells. Nature, 2004,432(7015):396一401. [16]Kondo T，Setoguchi T，Taga T,et al. Persistence of a small subpopulation of cancer sterrrlike cells in the C6 glioma cell line. Proceedings of the National A-cademy of Sciences,2004，101(3);781一786.

Metrics

Viewed

Full text

Abstract

Cited

Shared

Discussed