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-东南大学学报医学版

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

单位：湖北省肿瘤医院胸部放疗科, 湖北武汉 430079

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.

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