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辐射对肺腺癌细胞A549侵袭能力的影响及其分子机制
  • ISSN号:0254-5098
  • 期刊名称:《中华放射医学与防护杂志》
  • 时间:0
  • 分类:R734.2[医药卫生—肿瘤;医药卫生—临床医学]
  • 作者机构:[1]军事医学科学院放射与辐射医学研究所,北京100850, [2]中国疾病预防控制中心辐射防护与核安全医学所
  • 相关基金:基金项目:国家自然科学基金(81001216;30770640)
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4Gy1射线照射后A549细胞的侵袭能力,利用反转录PCR和Westernblot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4Gy^y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.O%和390.9%,差异均有统计学意义(F=111.7和596.7,P〈0.01)。照射后24hMMP-2mRNA及蛋白表达显著升高;照射后12h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,4Gy+AG490处理组的侵袭细胞数与单独4Gy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 T-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 (AC,490). 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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期刊信息
  • 《中华放射医学与防护杂志》
  • 北大核心期刊(2011版)
  • 主管单位:中国科学技术协会
  • 主办单位:中华医学会
  • 主编:
  • 地址:北京市德外新康街2号
  • 邮编:100088
  • 邮箱:cjrmp@cjrmp.sina.net
  • 电话:010-62389620
  • 国际标准刊号:ISSN:0254-5098
  • 国内统一刊号:ISSN:11-2271/R
  • 邮发代号:18-93
  • 获奖情况:
  • 国内外数据库收录:
  • 美国化学文摘(网络版),日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版),中国北大核心期刊(2000版)
  • 被引量:11741