STAT-3介导的非依赖VEGFR-2通路对NSCLC细胞放射敏感性影响的研究

doi:10.3760/cma.j.issn.1004-4221.2017.08.019

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Abstract Objective To investigate the effect of signal transducer and activator of transcription-3(STAT-3)-mediated non-dependent vascular endothelial growth factor receptor-2(VEGFR-2) pathway on the radiosensitivity of non-small cell lung cancer (NSCLC) cells and its possible mechanism. Methods NSCLC cells were divided into control group, apatinib (VEGFR-2 inhibitor) group, apatinib+S3I-201(STAT-3 inhibitor) group, radiation (RT) group, RT+apatinib group, and RT+apatinib+S3I-201 group. Q-PCR and Western blot were used to measure the mRNA and protein expression of VEGFR-2, STAT-3, other proteins involved in the signaling pathway, hypoxia-inducible factor 1α(HIF-1α), and cyclin D₁. The cellular radiosensitivity was determined by colony-forming assay and cell apoptosis and cell cycle distribution were evaluated by flow cytometry. Results For Calu-1 cells, there was no significant difference in the expression of VEGFR-2 mRNA and STAT-3 mRNA between the apatinib group and the control group (P>0.05);the apatinib group had significantly lower expression of HIF-1α mRNA and cyclin D₁ mRNA than the control group (P<0.05);the apatinib+S3I-201 group had significantly lower mRNA and phosphorylated protein expression of VEGFR-2, STAT-3, and related downstream target proteins than the control group (F=304.54, P<0.01;F=118.99, P<0.01, F=144.34, P<0.01;F=529.66, P<0.01);compared with the control group, the apatinib+S3I-201 group and the apatinib group showed increases in apoptosis rate and proportion of cells in G₂+M phase, and the apatinib+S3I-201 group had significantly greater increases than the apatinib group (F=72.37, P<0.01). Compared with Calu-1 cells, the radiosensitizing effect of apatinib on A549 cells was limited (SER[sensitizer enhancement ratio]=1.39). The radiosensitizing effect of apatinib+S3I-201 on A549 cells was significantly higher than that of apatinib (SER:1.72 vs. 1.39, P=0.000). Conclusions The inhibition of STAT-3 can enhance the radiosensitivity of NSCLC cells. When VEGFR-2 is inhibited by apatinib, activated STAT-3 regulates the expression of cyclin D₁ directly or indirectly to affect the radiosensitivity of NSCLC cells. The inhibition of VEGFR-2 and STAT-3 has a good radiosensitizing effect on NSCLC cells.

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	Articles by authors
	Liu Bin
	Hu Chenxi
	Liu Liang
	Liu Qingjing
	Tang Jingjiao
	Jiang Xiaodong

Key words： Protein express Lung meoplasms cell line Radiosensitivity

Received: 23 May 2016

Fund:National Natural Science Foundation of China (81472792)

Corresponding Authors: Jiang Xiaodong,Email:jxdysy1970@163.com

Cite this article:

Liu Bin,Hu Chenxi,Liu Liang et al. Effect of STAT-3-mediated non-dependent VEGFR-2 pathway on radiosensitivity of non-small cell lung cancer cells[J]. Chinese Journal of Radiation Oncology, 2017, 26(8): 938-944.

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http://journal12.magtechjournal.com/Jweb_fszlx/EN/10.3760/cma.j.issn.1004-4221.2017.08.019 OR http://journal12.magtechjournal.com/Jweb_fszlx/EN/Y2017/V26/I8/938

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