李峰生,高玲,刘丽卉,董波,罗庆良,陈肖华.辐射对肺腺癌细胞A549侵袭能力的影响及其分子机制[J].中华放射医学与防护杂志,2011,31(4):412-415
辐射对肺腺癌细胞A549侵袭能力的影响及其分子机制
Effect of ionizing radiation on invasiveness of pulmonary adenocarcinoma cells A549 and its mechanism
投稿时间:2011-04-10  
DOI:10.3760/cma.j.issn.0254-5098.2011.04.009
中文关键词:  辐射  肺腺癌  侵袭  基质金属蛋白酶-2  转录激活子3
英文关键词:Radiation  Pulmonary adenocarcinoma  Invasiveness  MMP-2  STAT3
基金项目:国家自然科学基金(81001216;30770640)
作者单位E-mail
李峰生 100850 北京,军事医学科学院放射与辐射医学研究所  
高玲 中国疾病预防控制中心辐射防护与核安全医学所  
刘丽卉 100850 北京,军事医学科学院放射与辐射医学研究所  
董波 100850 北京,军事医学科学院放射与辐射医学研究所  
罗庆良 100850 北京,军事医学科学院放射与辐射医学研究所  
陈肖华 100850 北京,军事医学科学院放射与辐射医学研究所 chenxiaohual@yahoo.com.cn 
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中文摘要:
      目的 探讨辐射对肺腺癌A549细胞侵袭能力的影响及其相关的分子机制。方法 用Transwell侵袭实验检测2和4 Gy γ射线照射后A549细胞的侵袭能力,利用反转录PCR和Western blot实验,检测基质金属蛋白酶-2(MMP-2) mRNA和蛋白及磷酸化STAT3蛋白表达水平。结果 2或4 Gy γ射线照射后,A549细胞的侵袭数量较未照射对照组分别升高了200.0%和390.9%,差异均有统计学意义(F=111.7和596.7,P<0.01)。照射后24 h MMP-2 mRNA及蛋白表达显著升高;照射后12 h信号转导子及转录激活子3 (STAT3)的磷酸化表达显著增加。使用特异性抑制剂AG490阻断STAT3磷酸化后,辐射诱导的MMP-2表达被显著抑制。同时,4 Gy+AG490处理组的侵袭细胞数与单独4 Gy照射组相比,减少了76.1% (F=555.9,P<0.01),仅为对照组的117.8%(F=3.6,P>0.05)。结论 辐射能通过激活STAT3来促进MMP-2的转录,最终导致A549细胞的侵袭能力增强。
英文摘要:
      Objective To investigate the effect of ionizing radiation on the invasion of the pulmonary adenocarcinoma cell line A549. Methods The invasiveness of A549 cells irradiated with 2 and 4 Gy doses of γ-rays was detected by using transwell invasion assay. The expression levels of matrix metalloproteinase (MMP)-2 mRNA and protein and phosphorylated signal transducers and activators of transcription 3 (STAT3) protein were detected by reverse transcription PCR and Western blot. Results After irradiation with 2 or 4 Gy, the invasiveness of A549 cells increased by 200.0% (F=111.7, P<0.01) and 390.9% (F=593.7, P<0.01), respectively, compared with that in untreated A549 cells. Furthermore, the transcription and protein expression of MMP-2 24 h after irradiation and the phosphorylation of STAT3 12 h after irradiation were promoted. The irradiation-induced elevation of MMP-2 protein expression was suppressed using STAT3 phosphorylation specific inhibitor (AG490). Moreover, compared with 4 Gy of irradiation alone, treatment with 4 Gy of irradiation plus AG490 decreased the number of invasive cells by 76.1% (F=555.9, P<0.01), and the number of invasive cells in 4 Gy of irradiation plus AG490 group made up only 117.8% of that in untreated group (F=3.6, P>0.05). Conclusions Ionizing radiation could activate STAT3, which triggers the transcription of MMP-2, and then promote the invasiveness of A549 cells.
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