[1]康 丹,吴朝蒙,曹润怿,等.根皮素引起前列腺癌LNCaP细胞发生凋亡的机制研究[J].南京师范大学学报(自然科学版),2017,40(02):43.[doi:10.3969/j.issn.1001-4616.2017.02.008]
　Kang Dan,Wu Zhaomeng,Cao Runyi,et al.Molecular Mechanism of Phloretin-Induced Apoptosisin Prostate Cancer LNCaP Cells[J].Journal of Nanjing Normal University(Natural Science Edition),2017,40(02):43.[doi:10.3969/j.issn.1001-4616.2017.02.008]
点击复制

根皮素引起前列腺癌LNCaP细胞发生凋亡的机制研究()
分享到：

《南京师范大学学报》（自然科学版）[ISSN:1001-4616/CN:32-1239/N]

卷:
第40卷
期数:
2017年02期
页码:
43
栏目:
·生命科学·
出版日期:
2017-06-29

文章信息/Info

Title:
Molecular Mechanism of Phloretin-Induced Apoptosisin Prostate Cancer LNCaP Cells
文章编号:
1001-4616(2017)02-0043-08
作者:
康 丹; 吴朝蒙; 曹润怿; 王方方; 田 倩; 刘 平
南京师范大学生命科学学院,江苏省分子与医学生物技术重点实验室,江苏 南京 210023
Author(s):
Kang Dan; Wu Zhaomeng; Cao Runyi; Wang Fangfang; Tian Qian; Liu Ping
School of Life Sciences,Nanjing Normal University,Jiangsu Key Laboratory for Molecular and Medical Biotechnology,Nanjing 210023,China
关键词:
根皮素; 细胞凋亡; 细胞周期; PI3K/AKT信号通路; 前列腺癌
Keywords:
phloretin; cell apoptosis; cell cycle; PI3K/AKT signal pathway; prostate cancer
分类号:
Q291
DOI:
10.3969/j.issn.1001-4616.2017.02.008
文献标志码:
A
摘要:
根皮素是存在于苹果、梨等水果及多种蔬菜汁液中的天然活性物质,具有抗肿瘤活性,能够有效地诱导细胞凋亡、抑制细胞增殖. 本研究初步探讨了根皮素诱导前列腺癌LNCaP细胞的凋亡和相关分子机制. 通过形态学观察、噻唑蓝(MTT)比色实验、CCK-8实验测定前列腺癌细胞活性; 采用DAPI染色法测定细胞核凝缩破裂; 运用Annexin V-FITC/PI双染流式细胞术测定前列腺癌细胞的凋亡率; 再通过PI单染流式细胞术测定前列腺癌细胞的周期变化; 以及采用Western blot检测PI3K/AKT信号通路及其下游细胞凋亡相关蛋白和细胞周期相关蛋白的表达. 实验结果表明:根皮素诱导前列腺癌LNCaP细胞周期阻滞在G2/M期,并呈浓度依赖性降低细胞活性、增加细胞核凝缩破裂,显著提高前列腺癌细胞的凋亡率. 在分子机制上,根皮素呈现浓度依赖性下调PI3K/AKT的活性,从而影响细胞凋亡相关蛋白和细胞周期相关蛋白的表达. 因此,根皮素对前列腺癌细胞的生长有显著的抑制作用,对治疗前列腺癌具有潜在的临床应用价值.
Abstract:
Phloretin,a natural product found in pears,apples and various vegetables,exerts anti-inflammatory,anti-oxidant and anti-tumor effects. Here,we investigated the molecular mechanism of phloretin-induced apoptosis in prostate cancer LNCaP cells. In this study,effects of phloretin on the viability of prostate cancer cells were investigated by morphological observation,MTT assay and CCK-8 assay,respectively. Effect of phloretin on apoptosis and cell cycle was measured by Flow Cytometry. Furthermore,western blot was employed to investigate the levels of phosphorylation of PI3K and AKT(the activity of PI3K/AKT signaling pathway); and check the expression of cell apoptosis-related and cell cycle-related proteins which were downstream of PI3K/AKT signaling pathway in LNCaP cells. As a result,we found that phloretin significantly blocked cell cycle arrest in G2/M phase by decreasing the protein level of Cyclin B1,and decreased the cell viability and increased the nuclear rupture in a dose-dependent manner; and finally resulted in a significantly apoptosis in LNCaP cells. In molecular level,phloretin showed a dose-dependent down-regulation of the activity of PI3K/AKT via down-regulating the phosphorylation of PI3K and AKT proteins,and then regulated the expression of cell apoptosis-related and cell cycle-related proteins. Therefore,phloretin significantly inhibited cell viability and promoted apoptosis in prostate cancer cells,suggesting that phloretin had potential clinical value for treatment of prostate cancer in clinic.

参考文献/References:

[1] ITO K. Prostate cancer in Asian men[J]. Nature reviews urology,2014,11(4):197.
[2]SIEGEL R L,MILLER K D,JEMAL A. Cancer statistics,2016[J]. Ca a cancer journal for clinicians,2016,66(1):7.
[3]CHOI B M,XIAO Y C,SHANG S G,et al. Anti-apoptotic effect of phloretin on cisplatin-induced apoptosis in HEI-OC1 auditory cells[J]. Pharmacological reports,2011,63(3):708-716.
[4]MIN J,LI X,HUANG K,et al. Phloretin induces apoptosis of non-small cell lung carcinoma A549 cells via JNK1/2 and p38 MAPK pathways[J]. Oncology reports,2015,34(6):2 871-2 879.
[5]KIM M S,KWON J Y,KANG N J,et al. Phloretin induces apoptosis in H-Ras MCF10A human breast tumor cells through the activation of p53 via JNK and p38 mitogen-activated protein kinase signaling[J]. Annals of the New York academy of sciences,2009,1171(1):479-483.
[6]WU C H,HO Y S,TSAI C Y,et al. In vitro and in vivo study of phloretin-induced apoptosis in human liver cancer cells involving inhibition of type Ⅱ glucose transporter[J]. International journal of cancer,2009,124(9):2 210-2 219.
[7]KOBORI M,IWASHITA K,SHINMOTO H,et al. Phloretin-induced apoptosis in B16 melanoma 4A5 cells and HL60 human leukemia cells[J]. Bioscience biotechnology and biochemistry,1999,63(4):719-725.
[8]SZLISZKA E,CZUBA Z P,MAZUR B,et al. Chalcones and dihydrochalcones augment TRAIL-mediated apoptosis in prostate cancer cells[J]. Molecules,2010,15(8):5 336.
[9]ADAMS J M,CORY S. The Bcl-2 protein family:arbiters of cell Survival[J]. Science,1998,281(5 381):1 322-1 326.
[10]冷向锋,程继义. TRAIL与前列腺癌[J]. 国际泌尿系统杂志,2003,23(3):231-233.
[11]TESTA J R,BELLACOSA A. AKT plays a central role in tumorigenesis[J]. Proc Natl Acad Sci USA,2001,98(20):10 983-10 985.
[12]GUANG H X,MICHAEL J,ALFONSO B,et al. Anti-apoptotic signaling by hepatocyte growth factor/Met via the phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways[J]. Proceedings of the national academy of sciences of the United States of America,2001,98(1):247.
[13]SUN H,KING A J,DIAZ H B,et al. Regulation of the protein kinase Raf-1 by oncogenic Ras through phosphatidylinositol 3-kinase,Cdc42/Rac and Pak[J]. Current biology,2000,10(5):281-284.

相似文献/References:

[1]许艳华,刘 津,陈华群.雷公藤红素抑制C2C12细胞增殖及诱导其凋亡[J].南京师范大学学报(自然科学版),2013,36(03):93.
　Xu Yanhua,Liu Jin,Chen Huaqun.Inhibition Effects of the Proliferation and Induction of the Apoptosis Of Celastrol In C2C12 Cells[J].Journal of Nanjing Normal University(Natural Science Edition),2013,36(02):93.
[2]彭琬昕,万燕雅,葛璐,等.siRNA干扰即刻早期基因Egr-1对汉防己甲素诱导的胰腺癌细胞自噬、凋亡的作用研究[J].南京师范大学学报(自然科学版),2015,38(03):71.
　PengWanxin,WanYanya,GeLu,et al.EffectofRNAInterferenceTargetingEgr-1InhibiteTetrandrine-InducedAutophagyandApoptosisofPancreaticPaTu8988Cellsinvitro[J].Journal of Nanjing Normal University(Natural Science Edition),2015,38(02):71.
[3]王　倩*,潘　望,李　伟*,等.Blf-ADT对HeLa细胞的抑制作用及其机制的研究[J].南京师范大学学报(自然科学版),2016,39(01):67.
　Wang Qian,Pan Wang,Li Wei,et al.Study on Anti-Tumor Activity and Mechanisms of Blf-ADT[J].Journal of Nanjing Normal University(Natural Science Edition),2016,39(02):67.
[4]刘振东,杨海芮,贾 薇,等.食药用真菌天然组分的抗肿瘤研究[J].南京师范大学学报(自然科学版),2018,41(01):108.[doi:10.3969/j.issn.1001-4616.2018.01.019]
　Liu Zhendong,Yang Hairui,Jia Wei,et al.The Antitumor Activity of Natural Components of Edible and Medicinal Fungi[J].Journal of Nanjing Normal University(Natural Science Edition),2018,41(02):108.[doi:10.3969/j.issn.1001-4616.2018.01.019]
[5]柏 骞,陈 露,常春洁,等.Ran对黑腹果蝇Kc细胞耐受DDT的影响[J].南京师范大学学报(自然科学版),2018,41(02):83.[doi:10.3969/j.issn.1001-4616.2018.02.015]
　Bo Qian,Chen Lu,Chang Chunjie,et al.Analysis of Ran and DDT Resistance in Drosophila Melanogaster Kc Cells[J].Journal of Nanjing Normal University(Natural Science Edition),2018,41(02):83.[doi:10.3969/j.issn.1001-4616.2018.02.015]
[6]抗晶晶,刘晓宁.线粒体ROS改变参与石蒜碱诱导的HepG2细胞凋亡[J].南京师范大学学报(自然科学版),2019,42(04):91.[doi:10.3969/j.issn.1001-4616.2019.04.013]
　Kang Jingjing,Liu Xiaoning.Mitochondrial ROS Contributes to Lycorine-inducedApoptosis in HepG2 Cells[J].Journal of Nanjing Normal University(Natural Science Edition),2019,42(02):91.[doi:10.3969/j.issn.1001-4616.2019.04.013]
[7]贺稳政,吴庆新,刘 平.NCAPD3激活AKT-FOXO信号通路抑制前列腺癌细胞的凋亡[J].南京师范大学学报(自然科学版),2021,44(03):90.[doi:10.3969/j.issn.1001-4616.2021.03.014]
　He Wenzheng,Wu Qingxin,Liu Ping.NCAPD3 Inhibits Apoptosis of Prostate Cancer Cellsby Activating AKT-FOXO Signaling Pathway[J].Journal of Nanjing Normal University(Natural Science Edition),2021,44(02):90.[doi:10.3969/j.issn.1001-4616.2021.03.014]
[8]乔晋宇,付思雨,陈明雪,等.二甲双胍联合热疗诱导U937细胞凋亡及其机制研究[J].南京师范大学学报(自然科学版),2024,(03):87.[doi:10.3969/j.issn.1001-4616.2024.03.011]
　Qiao Jinyu,Fu Siyu,Chen Mingxue,et al.Metformin Combined with Hyperthermia Induces Apoptosis in U937 Cells and Its Mechanisms[J].Journal of Nanjing Normal University(Natural Science Edition),2024,(02):87.[doi:10.3969/j.issn.1001-4616.2024.03.011]

备注/Memo

备注/Memo:
收稿日期:2016-10-15.
基金项目:国家自然科学基金(81272850、81472415).
通讯联系人:刘平,教授,博士生导师,研究方向:肿瘤发生与发展的分子机制. E-mail:08201@njnu.edu.cn
更新日期/Last Update: 2017-06-30