TGF-β/Akt/Smad signaling regulates ionizing radiation-induced epithelial-mesenchymal transition in acquired radioresistant lung cancer cells

Q1 Health Professions

Radiation Medicine and Protection Pub Date : 2022-09-01 DOI:10.1016/j.radmp.2022.05.003

Yongchun Zhou , Lingli Liao , Nan Su , Hua Huang , Yaoguo Yang , Yan Yang , Gengming Wang , Hongbo Xu , Hao Jiang

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引用次数: 0

Abstract

Objective

To define the properties of lung cancer cells that resisted conventionally fractionated radiation exposure.

Methods

Acquired radioresistant lung cancer cell line A549 was constructed by X-ray irradiation with a clinical conventional fraction dose of 2 Gy daily during 30 fractions. Cell morphology, molecular markers, migration capacity and invasion potential were evaluated by the microscope, Western blot, immunofluorescence, wound healing test and transwell chamber assay, respectively.

Results

Radioresistant A549 cells shifted from an epithelial to a mesenchymal morphology, termed as epithelial-mesenchymal transition (EMT), and was accompanied by decreased expressions of epithelial markers (F = 4.568, P < 0.05) and increased expression of mesenchymal markers (F = 4.270, P < 0.05), greater migratory and invasive capabilities (t = 6.386, 5.644, P < 0.05). The expression of TGF-β, and phosphorylated levels of Akt and Smad3 were also enhanced (F = 6.496, 4.685, 3.370, P < 0.05). Furthermore, the EMT phenotype induced by radiation could be reversed through inhibition of TGF-β, Akt or Smad3, indicating a functional relationship between them.

Conclusions

EMT mediates acquired radioresistance of lung cancer cells induced by IR with clinical parameters, and the crosstalk mode of TGF-β/Akt/Smad signaling plays a critical regulatory role in this process.

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TGF-β/Akt/Smad信号通路调控电离辐射诱导的获得性放射耐药肺癌细胞上皮-间质转化

目的探讨肺癌细胞抵抗常规分次辐射照射的特性。方法采用临床常规剂量每日2 Gy、连续照射30次的x线照射，获得肺癌耐药细胞株A549。分别采用显微镜、Western blot、免疫荧光、创面愈合试验和transwell室法评价细胞形态、分子标志物、迁移能力和侵袭潜力。结果耐辐射A549细胞由上皮细胞向间充质细胞转变，称为上皮-间充质转化(epithelial-mesenchymal transition, EMT)，并伴有上皮标志物表达降低(F = 4.568, P <0.05)，间充质标志物表达增加(F = 4.270, P <0.05)，更强的迁移和入侵能力(t = 6.386, 5.644, P <0.05)。TGF-β的表达、Akt和Smad3的磷酸化水平也显著升高(F = 6.496, 4.685, 3.370, P <0.05)。此外，辐射诱导的EMT表型可以通过抑制TGF-β、Akt或Smad3而逆转，表明它们之间存在功能关系。结论semt介导IR诱导肺癌细胞获得性放射耐药具有一定的临床参数，TGF-β/Akt/Smad信号串扰模式在该过程中起关键调控作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Radiation Medicine and Protection Health Professions-Emergency Medical Services

CiteScore

2.10

自引率

0.00%

发文量

审稿时长

103 days