| 毛绩伟,王喆,王漂,等.VEGFR2/STAT3/MMP-9介导阿帕替尼抑制辐射后鼻咽癌细胞迁移[J].中华放射医学与防护杂志,2019,39(7):481-486.Mao Jiwei,Wang Zhe,Wang Piao,et al.VEGFR2/STAT3/MMP-9 mediates apatinib-inhibited migration of nasopharyngeal carcinoma cells after radiation[J].Chin J Radiol Med Prot,2019,39(7):481-486 |
| VEGFR2/STAT3/MMP-9介导阿帕替尼抑制辐射后鼻咽癌细胞迁移 |
| VEGFR2/STAT3/MMP-9 mediates apatinib-inhibited migration of nasopharyngeal carcinoma cells after radiation |
| 投稿时间：2019-02-20 |
| DOI：10.3760/cma.j.issn.0254-5098.2019.07.001 |
| 中文关键词: 鼻咽癌 阿帕替尼 迁移 基质金属蛋白酶 上皮间质转化 |
| 英文关键词:Nasopharyngeal carcinoma Apatinib Migration MMP-9 EMT |
| 基金项目:国家自然科学基金（81501753） |
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| 中文摘要: |
| 目的 探讨阿帕替尼对X射线照射后鼻咽癌细胞迁移能力的影响及机制。方法 通过划痕实验比较人永生化鼻咽上皮细胞（NP69）和鼻咽癌细胞（CNE-1、CNE-2）的迁移能力，以及不同浓度阿帕替尼（0、5、10和15 μmol/L）对其的影响；通过CCK-8检测阿帕替尼对鼻咽癌细胞活性的影响，确定药物干预浓度；将鼻咽癌细胞分为对照组、阿帕替尼组（15 μmol/L）、照射组和阿帕替尼联合照射组，检测各组迁移能力；通过Western blot检测各实验组磷酸化血管内皮细胞生长因子受体2（pVEGFR2）、磷酸化信号传导及转录激活因子（pSTAT3）、STAT3、基质金属蛋白酶（MMP-9）和上皮间质转化（EMT）相关信号通路激活与蛋白表达的变化。结果 与人永生化鼻咽上皮细胞（NP69）相比，鼻咽癌细胞CNE-1和CNE-2迁移能力明显更强（t=-5.759、-16.578，P<0.05）；与对照组相比，鼻咽癌细胞在阿帕替尼（5、10和15 μmol/L）干预后迁移能力明显降低，并具有剂量依赖性（t=2.804~13.362，P<0.05）；与照射组相比，阿帕替尼联合照射组的鼻咽癌细胞划痕愈合速率降低（t=5.932、2.791，P<0.05），说明阿帕替尼可以明显抑制X射线照射后鼻咽癌细胞的迁移；Western blot结果显示，鼻咽癌细胞经过阿帕替尼处理后，磷酸化的VEGFR2和STAT3表达显著下降，同时，MMP-9蛋白表达明显下降，EMT相关蛋白发生变化。结论 阿帕替尼可能通过下调VEGFR2/STAT3/MMP-9信号通路抑制鼻咽癌细胞EMT化，从而抑制X射线照射后鼻咽癌细胞的迁移。 |
| 英文摘要: |
| Objective To investigate the effect of apatinib on the migration ability of nasopharyngeal carcinoma NPC cells after X-ray irradiation and involved protein expressions. Methods The migration abilities of human immortalized nasopharyngeal epithelial cells (NP69) and nasopharyngeal carcinoma cells (CNE-1, CNE-2) treated with different concentrations of apatinib (0, 5, 10 and 15 μmol/L) were compared by wound healing assay. The effect of apatinib on the activity of NPC cells was detected by CCK-8 for determining the suitable intervention concentration of apatinib. Then NPC cells were divided into control group, apatinib group (15 μmol/L), X-ray irradiation group and apatinib combined with X-ray irradiation group, and the migration ability of each group was compared by wound healing assay. The expressions of pVEGFR2, pSTAT3, STAT3, MMP-9 and EMT related proteins were detected by western blot. Results Compared with the NP69, the migration abilities of CNE-1 and CNE-2 were significantly enhanced (t=-5.759, -16.578, P<0.05). Compared with the control group (0 μmol/L), the migration ability of NPC cells after treatment with apatinib(5, 10 and 15 μmol/L)was significantly decreased in a concentration dependent manner (t=2.804-13.362, P<0.05). Compared with the X-ray irradiation group, the wound healing rate of NPC cells in the apatinib combined with X-ray irradiation group was decreased (t=5.932, 2.791, P<0.05), indicating that apatinib can significantly inhibit the migration of NPC cells after X-ray irradiation. Western blot assay showed that the expressions of pVEGFR2 and pSTAT3 were significantly decreased in NPC cells treated with apatinib, meanwhile, the expression of MMP-9 protein was significantly decreased, and the EMT-related protein was changed. Conclusions Apatinib inhibits migration of X-ray irradiated NPC cells by inhibiting EMT through down-regulating VEGFR2/STAT3/MMP-9 signaling pathway. |
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