| 孙健,刘宁波,庄洪卿,赵路军,袁智勇,王平.厄洛替尼和塞来昔布联合应用对人肺腺癌 A549细胞放射增敏的研究[J].中华放射医学与防护杂志,2012,32(2):186-190 |
| 厄洛替尼和塞来昔布联合应用对人肺腺癌 A549细胞放射增敏的研究 |
| Enhancement of radiation sensitivity by erlotinib and celecoxib in A549 human lung cancer cell line |
| 投稿时间：2010-05-19 |
| DOI：10.3760/cma.j.issn.0254-5098.2012.02.020 |
| 中文关键词: 塞来昔布|厄洛替尼|肺腺癌细胞|放射增敏 |
| 英文关键词:Celecoxib|Erlotinib|Lung adenocarcinoma|Radiosensitization |
| 基金项目: |
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| 中文摘要: |
| 目的 探讨联合应用厄洛替尼和塞来昔布阻断表皮生长因子受体和环氧化酶-2受体对人肺腺癌A549细胞株的放射增敏效应及机制。方法 四甲基偶氮唑盐(MTT)比色法检测厄洛替尼和塞来昔布的IC20作为后续实验浓度。体外培养克隆形成实验检测厄洛替尼和塞来昔布联合或不联合X射线对人肺腺癌A549细胞的作用,计算其存活分数,绘制细胞存活曲线。流式细胞术检测细胞凋亡和细胞周期的变化,Western blot检测Akt和pAkt的表达。结果 厄洛替尼和塞来昔布的IC20分别为(5.15±0.14)和(40.32±1.26) μmol/L。照射+联合用药组的Dq、D0及 SF2均明显低于单纯照射组、照射+塞来昔布组及照射+厄洛替尼组(t=6.62,P<0.05);照射+联合用药组、照射＋厄洛替尼组和照射＋塞来昔布组的SER为2.217、1.503和1.299。厄洛替尼和塞来昔布与射线联合作用后,使S期细胞比例减少,联合用药组作用更明显。药物作用前后及药物增敏照射后Akt在蛋白表达水平没有明显改变;塞来昔布和厄洛替尼均能抑制pAkt的表达,照射能够略提高pAkt蛋白的表达,与单纯照射组相比,塞来昔布或厄洛替尼联合照射组pAkt蛋白的表达减低,两药联用并联合照射组pAkt蛋白的表达最低(t=4.89,P<0.05)。结论 厄洛替尼和塞来昔布各自均有放射增敏作用,两药联合应用可以进一步提高放射增敏效应。其机制涉及到使细胞周期中对射线不敏感的S期细胞减少到最低,并进一步增强了射线诱导的凋亡。 |
| 英文摘要: |
| Objective To investigate the role of epidermal growth factor receptor and cyclooxygenase-2 pathways in the erlotinib and celecoxib enhanced radiation sensitivity in A549 human lung cancer cell line. Methods IC20 of erlotinib and celecoxibon in A549 human lung cancer cells was measured by MTT assay. Clonogenic assays were used to evaluate the antitumor effects of the drugs and X-irradiation. Flow cytometry was used to assess the apoptosis and cell cycle alteration, and Western blot was used for the detection of Akt and phospho-Akt. Results Both erlotinib and celecoxib could inhibit the proliferation of A549 cells in vitro in a dose-dependent manner and their values of IC20 were (5.15±0.14) and (40.32±1.26) μmol/L, respectively. For radiation survival, the values of Dq,D0,SF2 of the combination of two drugs were lower than those of either drug (t=6.62, P<0.05).The SER of celecoxib, erlotinib and their combination were 1.299, 1.503 and 2.217, respectively. Flow cytometry assay showed that both celecoxib and erlotinib could enhance radiation-induced G0 /G1 arrest, reduce the cell numbmer in S phase,and enhance radiation-induced apoptosis, especially for the combination of drugs. Western blot assay showed that the expressions of Akt protein were similar in all groups. However, pAkt expression was suppresssed by erlotinib and celecoxib, but promoted by radiation. pAkt had the lowest expression in the radiated cells with the treatment of two drugs (t=4.89, P<0.05). Conclusions The erlotinib and/or celecoxib could enhance radiosensitivity probably by increasing cell apoptosis and reducing the number of S-phase cells with low radiosensitivity. |
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