VEGFR2/STAT3/MMP-9 mediates apatinib-inhibited migration of nasopharyngeal carcinoma cells after radiation
10.3760/cma.j.issn.0254-5098.2019.07.001
- VernacularTitle:VEGFR2/STAT3/MMP-9介导阿帕替尼抑制辐射后鼻咽癌细胞迁移
- Author:
Jiwei MAO
1
;
Zhe WANG
;
Piao WANG
;
Shanshan LIANG
;
Zaishuang JU
;
Liang YANG
;
Longyu CAI
;
Ruoyu WANG
Author Information
1. 大连大学附属中山医院肿瘤科 116001
- Keywords:
Nasopharyngeal carcinoma;
Apatinib;
Migration;
MMP-9;
EMT
- From:
Chinese Journal of Radiological Medicine and Protection
2019;39(7):481-486
- CountryChina
- Language:Chinese
-
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.
