| Mao Jiwei,Wang Zhe,Wang Piao,Liang Shanshan,Ju Zaishuang,Yang Liang,Cai Longyu,Wang Ruoyu.VEGFR2/STAT3/MMP-9 mediates apatinib-inhibited migration of nasopharyngeal carcinoma cells after radiation[J].Chinese Journal of Radiological Medicine and Protection,2019,39(7):481-486 |
| VEGFR2/STAT3/MMP-9 mediates apatinib-inhibited migration of nasopharyngeal carcinoma cells after radiation |
| Received:February 20, 2019 |
| DOI：10.3760/cma.j.issn.0254-5098.2019.07.001 |
| KeyWords:Nasopharyngeal carcinoma Apatinib Migration MMP-9 EMT |
| FundProject:国家自然科学基金（81501753） |
| Author Name | Affiliation | E-mail | | Mao Jiwei | Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China | | | Wang Zhe | Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China | | | Wang Piao | Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China | | | Liang Shanshan | The Key Laboratory of Biomarker High Throughput Screening and Target Translation of Breast and Gastrointestinal Tumor, Dalian 116001, China | | | Ju Zaishuang | Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China | | | Yang Liang | Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China | | | Cai Longyu | Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China | | | Wang Ruoyu | Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China | wangruoyu1963@163.com |
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| Abstract:: |
| 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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