nav emailalert searchbtn searchbox tablepage yinyongbenwen piczone journalimg journalInfo journalinfonormal searchdiv searchzone qikanlogo popupnotification paper paperNew
2018, 07, v.37 3238-3244
三氧化二砷对人乳腺癌MCF-7细胞的抑制作用及其FOXO1表达的影响
基金项目(Foundation): 安徽省教育厅自然科学研究重点项目(KJ2015A289);; 蚌埠医学院自然科学基金重点项目(BYKY1405ZD,BYKY1421ZD)共同资助
邮箱(Email):
DOI: 10.13417/j.gab.037.003238
摘要:

本研究探讨三氧化二砷对人乳腺癌MCF-7细胞的生长及迁移等作用的抑制作用以及对FOXO1的表达的影响。不同浓度三氧化二砷作用人乳腺癌MCF-7细胞后,利用MTT法检测细胞增殖、流式细胞术检测细胞凋亡的变化;通过划痕实验和transwell侵袭实验检测细胞迁移和侵袭能力的变化;通过荧光定量PCR和Western blotting检测FOXO1基因和蛋白水平表达的变化。结果显示不同浓度的三氧化二砷能够抑制细胞生长、迁移及侵袭,诱导细胞发生凋亡,且具有浓度依赖性;并且三氧化二砷可以上调FOXO1基因和蛋白水平的表达。因此三氧化二砷对人乳腺癌MCF-7细胞的抑制作用可能与上调抑癌基因FOXO1表达有关。

Abstract:

To explore the effect of arsenic trioxide on cell growth inhibition, cell migration inhibition and the expression of FOXO1 in human breast cancer MCF-7 cells. the human breast cancer MCF-7 cells were treated with the different concentrations of arsenic trioxide in vitro. The cell proliferation were detected by MTT assay, and cell apoptosis were analyzed by flow cytometry. furthermore, the cell migration and invasion capacity were analyzed by the wound healing assay and the transwell assay. Moreover, the expression of FOXO1 gene and protein were tested by Real-time-PCR and western blotting assay. Arsenic trioxide suppressed the cell growth, migration and invasion with dose-dependent manner in MCF-7 cells. arsenic trioxide also induced the cell apoptosis with dose-dependent manner in MCF-7 cells. And the gene and protein expression of FOXO1 were up-regulated in a dose-dependent manner. The inhibition effect of arsenic trioxide on human breast cancer MCF-7 cells may be related with the up-regulation of FOXO1 expression.

参考文献

Chang K.J.,Yang M.H.,Zheng J.C.,Li B.,and Nie W.,2016,Arsenic trioxide inhibits cancer stem-like cells via down-regulation of Gli1 in lung cancer,Am.J.Transl.Res.,8(2):1133-1143

Cui L.M.,Gao B.,Cao Z.G.,Chen X.Y.,Zhang S.D.,and Zhang W.Z.,2016,Downregulation of B7-H4 in the MHCC97-h epatocellular carcinoma cell line by arsenic trioxide,Mol.Med.Rep.,13(3):2032-2038

Carbajo-Pescador S.,Mauriz J.L.,García-Palomo A.,and González-Gallego J.,2014,Fox O proteins:regulation and molecular targets in liver cancer,Current Medicinal Chemistry,21:1231-1246

Jadhav V.,Ray P.,Sachdeva G.,and Bhatt P.,2016,Biocompatible arsenic trioxide nanoparticles induce cell cycle arrest by p21(WAF1/CIP1)expression via epigenetic remodeling in LNCa P and PC3 cell lines,Life Sci.,148:41-52

Ko Y.S.,Cho S.J.,Park J.,Kim Y.,Choi Y.J.,Pyo J.S.,Jang B.G.,Park J.W.,Kim W.H.,and Lee B.L.,2015,Loss of FOXO1promotes gastric tumour growth and metastasis through upregulation of human epidermal growth factor receptor 2/neu expression,Br.J.Cancer,113(8):1186-1196

Prasad S.B.,Yadav S.S.,Das M.,Govardhan H.B.,Pandey L.K.,Singh S.,Pradhan S.,and Narayan G.,2014,Down regulation of FOXO1 promotes cell proliferation in cervical cancer,J.Cancer,5(8):655-662

Shi Y.,Hu B.,Guo Y.,Wang H.,and Xia J.,2012,Inhibitory mechanism on growth of MA-891 cells by arsenic trioxide,Zhongguo Zhongyao Zazhi,37(5):637-642(石莹,胡博,郭俣,王慧,夏俊,2012,三氧化二砷抑制小鼠乳腺癌细胞MA-891生长作用及其对端粒酶活性的影响,中国中药杂志,37(5):637-642)

Salazar M.,Lorente M.,García-Taboada E.,Pérez Gómez E.,Dávila D.,Zú觡iga-García P.,Flores J.,Rodríguez A.,Hegedus Z.,Mosén-Ansorena D.,Aransay A.,Hernández-Tiedra S.,López-Valero I.,Quintanilla M.,Sánchez C.,Iovanna J.,Dusetti N.,Guzmán M.,Francis S.,Carracedo A.,Kiss-Toth E.,and Velasco G.,2015,TRIB3 suppresses tumorigenesis by controlling m TORC2/AKT/FOXO signaling,Mol.Cell.Oncol.,2(3):e980134

Wang G.Z.,Zhang W.,Fang Z.T.,Zhang W.,Yang M.J.,Yang G.W.,Li S.,Zhu L.,Wang L.L.,Zhang W.S.,Liu R.,Qian S.,Wang J.H.,and Qu X.D.,2014,Arsenic trioxide:marked suppression of tumor metastasis potential by inhibiting the transcription factor Twist in vivo and in vitro,J.Cancer Res.Clin.Oncol.,140(7):1125-1136

Wu Y.Y.,Elshimali Y,Sarkissyan M,Mohamed H,Clayton S,and Vadgama J.V.,2012,Expression of FOXO1 is associated with GATA3 and Annexin-1 and predicts disease-free survival in breast cancer,Am.J.Cancer Res.,2(1):104-115

Zheng L.,Jiang H.,Zhang Z.W.,Wang K.N.,Wang Q.F.,Li Q.L.,and Jiang T.,2016,Arsenic trioxide inhibits viability and induces apoptosis through reactivating the Wnt inhibitor secreted frizzled related protein-1 in prostate cancer cells,Oncotargets Ther.,9:885-894

Zhang S.,Ma C.,Pang H.,Zeng F.,Cheng L.,Fang B.,Ma J.,Shi Y.,Hong H.,Chen J.,Wang Z.,and Xia J.,2016,Arsenic trioxide suppresses cell growth and migration via inhibition of mi R-27a in breast cancer cells,Biochem.Biophys.Res.Commun,469(1):55-61

Zhou W.C.,Cheng L.,Shi Y.,Ke S.Q.,Huang Z.,Fang X.G.,Chu C.W.,Xie Q.,Bian X.W.,Rich J.N.,and Bao S.D.,2015,Arsenic trioxide disrupts glioma stem cells via promoting PML degradation to inhibit tumor growth,Oncotarget,6(35):37300-37315

Zhang H.J.,Pan Y.Q.,Zheng L.,Choe C.,Lindgren B.,Jensen E.,Westendorf J.,Cheng L.,and Huang H.J.,2011,FOXO1 inhibits Runx2 transcriptional activity and prostate cancer cell migrationand invasion,Cancer Res.,71(9):3257-3267

基本信息:

DOI:10.13417/j.gab.037.003238

中图分类号:R737.9

引用信息:

[1]石莹,连超群,曾凡鹏,等.三氧化二砷对人乳腺癌MCF-7细胞的抑制作用及其FOXO1表达的影响[J].基因组学与应用生物学,2018,37(07):3238-3244.DOI:10.13417/j.gab.037.003238.

基金信息:

安徽省教育厅自然科学研究重点项目(KJ2015A289);; 蚌埠医学院自然科学基金重点项目(BYKY1405ZD,BYKY1421ZD)共同资助

发布时间:

2018-07-25

出版时间:

2018-07-25

检 索 高级检索