| 周菊英,徐晓婷,李晓庆,王利利,秦颂兵,涂彧.塞来昔布对人肺腺癌细胞株A549的放射增敏效应及细胞迁移力的影响[J].中华放射医学与防护杂志,2010,30(5):564-567 |
| 塞来昔布对人肺腺癌细胞株A549的放射增敏效应及细胞迁移力的影响 |
| Radiosensitization of celecoxib on human lung adenocarcinoma cell line A549 and inhibition of migration ability in vitro |
| 投稿时间：2009-10-12 |
| DOI： |
| 中文关键词: 肺肿瘤 放射增敏 COX-2 MMP-2 |
| 英文关键词:Lung neoplasms Radiosensitivity Cyclo-oxygenase-2 (COX-2) Metalloproteinase-2 (MMP-2) |
| 基金项目:江苏高校省级重点实验室开放研究课题(KJS0723) |
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| 中文摘要: |
| 目的 观察选择性COX-2抑制剂塞来昔布(celecoxib)对人肺腺癌细胞株A549的放射增敏效应及抑制细胞迁移力的作用。方法 选用人肺腺癌细胞株A549作为研究对象。选择适当浓度的塞来昔布,设置对照组、药物组、单纯放射组和放射加药组,成克隆分析法测定塞来昔布对细胞的放射增敏效应,细胞划痕试验观察A549细胞的迁移力,酶联免疫吸附实验(ELISA)检测细胞培养上清液中基质金属蛋白酶(MMP)-2的含量。结果 细胞划痕试验结果显示,放射加药组比单纯放射组和药物组的无细胞划痕区均增宽,细胞迁移力均明显下降,且随着药物浓度的增加,抑制细胞迁移的能力增强。30和50 μmol/L 塞来昔布对A549细胞显示出浓度依赖性放射增敏作用,放射加药与单纯放射组相比, SF2、D0、D\-q出现不同程度的下调。ELISA检测发现,细胞培养上清液中MMP-2的含量,药物组较对照组,放射加药组较单纯放射组均明显下降(t=3.78、5.79,P<0.05),但单纯放射组和对照组对细胞分泌MMP-2的抑制效应不明显(t=2.73、2.38,P>0.05)。结论 塞来昔布在体外试验中对肺腺癌细胞株A549具有浓度依赖性放射敏感性,机制可能为降低了细胞对放射的亚致死损伤修复能力。塞来昔布可能通过抑制A549细胞分泌MMP-2,从而抑制细胞的迁移能力。 |
| 英文摘要: |
| Objective To investigate the effects of radiosensitivity enhancement and inhibition of migration ability of human lung adenocarcinoma cells by celecoxib, a selective cyclooxygenase(COX)-2 inhibitor.Methods Human lung adenocarcinoma cells of the line A549 were cultured and then inoculated into six-well plates and randomly divided into 4 groups:control group, celecoxib group administered with celecoxib at the subtoxic doses 30 and 50 μmol/L, irradiated group exposed to 0, 1, 2, 4, 6, or 8 Gy by linear accelerator, and combined treatment (celecoxib+irradiation) group. The radiosensitizing effect of celecoxib was assessed by clonogenic cell survival test.The migration ability of the A549 cells was measured by scratch-wound test and the content of metalloproteinase-2 (MMP-2) in culture supernatant was detected with ELISA.Results The sensitization enhancement ratio of the celexib group was increased dose-dependently. The values of D0, Dq, SF-2 and D0.01 of the celecoxib+irradiation group were all significantly lower than those of the irradiated group. Scratch-wound test showed that the no-scratch area of the celecoxib+irradiation group and celecoxib group were all significantly wider than those of the mere irradiation and control groups and there was a dose-dependent manner, and the no-scratch area of the celecoxib+irradiation group was wlider than that of the celecoxib group. ELISA showed that the MMP-2 levels in the supernatant of the celecoxib group and celecoxib+irradiation group were respectively significantly lower than those of the control group and mere irradiated group (t=3.78, 5.79、3.15, P<0.05), however, there was not significant difference between the mere irradiation and control groups(t=2.73, 2.38,P>0.05).Conclusions Celecoxib enhances concentration-dependently the radiosensitivity of human lung carcinoma cell and inhibits the secretion of MMP-2 of the carcinoma cells, thus inhibiting their migration ability. |
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