>
网站首页期刊介绍通知公告编 委 会投稿须知电子期刊广告合作联系我们
最新消息:
外源性信号素3A信号通路对转化生长因子-β1诱导肺癌细胞侵袭、增殖的影响
作者:罗燕  徐崇明  段丽群 
单位:湖北省肿瘤医院 胸部放疗科, 湖北 武汉 430079
关键词:肺癌 外源性信号素3A 信号通路 转化生长因子-β1 Akt磷酸化 
分类号:R734.2
出版年·卷·期(页码):2017·36·第四期(609-614)
摘要:

目的:探讨外源性信号素3A(Sema 3A)信号通路对转化生长因子-β1(TGF-β1)诱导的肺癌A549细胞侵袭、增殖的影响及可能作用机制。方法:将肺癌A549细胞分为3组,即空白对照组、TGF-β1诱导组(TGF-β1组)、Sema 3A预处理组(Sema 3A+TGF-β1组)。空白对照组细胞正常培养;TGF-β1组加入5 μg·L-1 TGF-β1;Sema 3A+TGF-β1组首先加入10 μmol·L-1 Sema 3A,预处理40~50 min后再加入5 μg·L-1 TGF-β1。检测细胞增殖、侵袭能力和E-cadherin、Akt、P-Akt蛋白表达。结果:Sema 3A+TGF-β1组细胞Sema 3A mRNA相对表达水平显著高于空白对照组和TGF-β1组(均P<0.05)。培养36 h~72 h内,TGF-β1组细胞增殖率显著高于Sema 3A+TGF-β1组和空白对照组(均P<0.05),Sema 3A+TGF-β1组细胞增殖率显著高于空白对照组(均P<0.05)。TGF-β1组穿透滤膜细胞数显著高于Sema 3A+TGF-β1组和空白对照组(均P<0.05),Sema 3A+TGF-β1组穿透滤膜细胞数显著高于空白对照组(P<0.05)。TGF-β1组E-cadherin蛋白表达显著低于Sema 3A+TGF-β1组和空白对照组(均P<0.05),P-Akt蛋白显著高于Sema 3A+TGF-β1组和空白对照组(均P<0.05);Sema 3A+TGF-β1组E-cadherin蛋白表达显著低于空白对照组(P<0.05),P-Akt显著高于空白对照组(P<0.05)。结论:Sema 3A能够抑制TGF-β1诱导肺癌细胞侵袭、增殖的效应,其机制可能与抑制Akt磷酸化、上调E-cadherin表达有关。

Objective:To explore the effect of semaphorin 3A (Sema 3A) signaling pathway on invasion and proliferation of lung cancer cells induced by transforming growth factor -β1 (TGF-β1) and its mechanisms. Methods:The lung cancer A549 cells were divided into three groups:blank control group (control), TGF-β1 induced group (TGF-β1), 3A Sema pretreatment group (Sema 3A+TGF-β1). The control group was cultured with normal cultured, 5 μg·L-1 TGF-β1 was added in TGF-β1 group, 10 μmol·L-1 of Sema 3A was firstly added and pretreated for 40-50 min and then 5 μg·L-1 of TGF-β1 added in the Sema 3A+TGF-β1 group. Cell proliferation, invasion ability and the expression level of E-cadherin, Akt, P-Akt protein was measured. Results:After Sema 3A pretreatment, the Sema 3A+TGF-β1 group cells were round or oval. Sema 3A mRNA relative expression level in Sema 3A+TGF-β1 group were significantly higher than that in the control group and the TGF-β1 group(P<0.05). In 36-72 h, the proliferation rate of TGF-β1 group was significantly higher than in Sema 3A+TGF-β1 group and the control group(P<0.05), the proliferation rate in Sema 3A+TGF-β1 group was significantly higher than that in the control group(P<0.05). The migrated cells number was significantly higher than that in Sema 3A+TGF-β1 group and the control group(P<0.05),migrated cell number in Sema 3A+TGF-β1 group was significantly higher than that in the control group(P<0.05). The expression of E-cadherin protein was significantly lower than that in Sema 3A+TGF-β1 group and the control group, P-Akt protein was significantly higher than that in Sema 3A+TGF-β1 group and the control group(P<0.05). E-cadherin protein in Sema 3A+TGF-β1 group was significantly lower than that in the control group, P-Akt protein was significantly higher than that in the control group(P<0.05). Conclusion:Sema 3A can inhibit invasion and proliferation induced by TGF-β1, the mechanism may be related to the inhibition of Akt phosphorylation and up regulation of E-cadherin expression.

参考文献:

[1] YINGJIE L,JIAN T,CHANGHAI Y,et al.Numblike regulates proliferation,apoptosis,and invasion of lung cancer cell[J].Tumour Biol,2013,34(5):2773-2780.
[2] GUPTA G P,MASSAGUÉ J.ID genes mediate tumor reinitiation during breast cancer lung metastasis[J].Proc Natl Acad Sci U S A,2007,104(49):19506-19511.
[3] KIM S J,CHUNG T W,CHOI H J,et al.Ganglioside GM3 participates in the TGF-β1-induced epithelial-mesenchymal transition of human lens epithelial cells[J].Biochem J,2013,449(1):241-251.
[4] MAIONE F,CAPANO S,REGANO D,et al.Semaphorin 3A overcomes cancer hypoxia and metastatic dissemination induced by antiangiogenic treatment in mice[J].J Clin Invest,2012,122(5):1832-1848.
[5] ZHOU H,AIPING W U,WEI F U,et al.Significance of semaphorin-3A and MMP-14 protein expression in non-small cell lung cancer[J].Oncol Lett,2014,7(5):1395-1400.
[6] MISHRA R,THORAT D,SOUNDARARAJAN G,et al.Semaphorin 3A upregulates FOXO 3a-dependent MelCAM expression leading to attenuation of breast tumor growth and angiogenesis[J].Oncogene,2014,34(12):1584-1595.
[7] MONY S,LEE S J,HARPER J F,et al.Regulation of Na,K-ATPase β1-subunit in TGF-β2-mediated epithelial-to-mesenchymal transition in human retinal pigmented epithelial cells[J].Exp Eye Res,2013,115:113-122.
[8] 邓陶然,林丹丹,钟波,等.TGF-α、TGF-β1、TIMP-2 mRNA在非小细胞肺癌中的表达及临床意义[J].临床肺科杂志,2016,21(11):2063-2067.
[9] HUANG S,HÖLZEL M,KNIJNENBURG T,et al.MED12 controls the response to multiple cancer drugs through regulation of TGF-β receptor signaling[J].Cell,2012,151(5):937-950.
[10] 王强,王佩佩,孟萍萍,等.强化训练对脑缺血再灌注大鼠臂板蛋白3A及其受体神经纤毛蛋白-1表达的影响[J].中华物理医学与康复杂志,2012,34(1):2-7.
[11] KACZMAREK J S,CLAPHAM D E.Calpain cleaves and activates the TRPC5 channel to participate in semaphorin 3A-induced neuronal growth cone collapse[J].Proc Natl Acad Sci U S A,2012,109(20):7888-7892.
[12] VENKOVA K,CHRISTOV A,KAMALUDDIN Z,et al.Semaphorin 3A signaling through neuropilin-1 is an early trigger for distal axonopathy in the SOD1G93A mouse model of amyotrophic lateral sclerosis[J].J Neuropathol Exp Neurol,2014,73(7):702-713.
[13] CASAZZA A,FU X,JOHANSSON I,et al.Systemic and targeted delivery of semaphorin 3A inhibits tumor angiogenesis and progression in mouse tumor models[J].Arterioscler Thromb Vasc Biol,2011,31(4):741-749.
[14] HOSAKA S,HORIUCHI K,YODA M,et al.A novel multi-kinase inhibitor pazopanib suppresses growth of synovial sarcoma cells through inhibition of the PI3K-AKT pathway[J].J Orthop Res,2012,30(9):1493-1498.
[15] VADASZ Z,HAJ T,HALASZ K,et al.Semaphorin 3A is a marker for disease activity and a potential immunoregulator in systemic lupus erythematosus[J].Arthritis Res Ther,2012,14(3):R146.
[16] 崔凤鸣,朱海涛,包善华,等.骨髓间充质干细胞作为胰腺癌基因治疗载体的实验研究[J].现代医学,2011,39(4):387-392.
[17] 匡小跟,张晖辉,许韩峰,等.钙黏蛋白E、桥粒芯糖蛋白2、磷酸化Akt和转录因子Snail在侵袭性前列腺癌中的作用[J].中国现代医学杂志,2016,26(8):38-43.

服务与反馈:
文章下载】【发表评论】【查看评论】【加入收藏
提示:您还未登录,请登录!点此登录
您是第 231219 位访问者


copyright ©《东南大学学报(医学版)》编辑部
联系电话:025-87232481 83272483
电子邮件:
bjb@pub.seu.edu.cn

苏ICP备09058364