临床与实验病理学杂志2017，Vol.33Issue(5)：490-496,7.DOI:10.13315/j.cnki.cjcep.2017.05.005
骨肉瘤中Axl抑制凋亡及与凋亡蛋白的相关性
Relationship between receptor tyrosine kinase Axl and apoptosis relative proteins in osteosarcoma
摘要
Abstract
Purpose To identify the role of tyrosine kinase receptor Axl for anti-apoptosis which was induced by cisplatin (DDP) and methotrexate (MTX) chemotherapy and to analyze the relationship between P-Axl and apoptosis-related proteins in osteosarcoma.Methods Osteosarcoma cell lines MG63,143B and U2OS were used in apoptosis assays,Axl siRNA transfection,cytotoxicity assays,cell cycle analysis,etc.A total of 41 cases of osteosarcom patients were included for immunohistochemistry of EnVision two-step staining and clinico-pathological relative analysis.TUNEL assay was performed in ten cases for apoptosis detection.Results Among the osteosarcoma cell lines,Gas6/Axl could obviously protect tumor cells from apoptosis induced by DDP and MTX (P ＜ 0.05).Axl siRNA transfection enhanced cell apoptosis,whereas Gas6 prone to function upon previous knockdown by Axl siRNA.Among the 41 cases,the positive rate of P-Axl,BCL-2,and Bax was 85.4％,70.7％,and 36.6％,respectively.In contrast,the positive rate of them was 22.2％,11.1％,and 11.1％ in osteofibrous dysplasia,respectively.The expression levels of these apoptosisrelated factors were significantly higher in osteosarcoma than in osteofibrous dysplasia (P ＜ 0.05).Through clinico-pathological analysis,there were significant relationships between the survival status and BCL-2 or Bax expression (P ＜ 0.05).Pearson correlation analysis demonstrated that BCL-2 was positively correlated to P-Axl with statistical significance (r =0.842,P ＜ 0.0001).By Cox univariate analysis,BCL-2 or Bax was correlated with the patients' prognosis.TUNEL assay also demonstrated that P-Axl high expression inhibited apoptosis in osteosarcoma tissues.Conclusion Gas6/Axl protects osteosarcoma cells from the apoptosis induced by DDP and MTX chemotherapy and inhibits apoptosis in osteosarcoma tissue,possibly through the regulation of apoptosis-related protein BCL-2.关键词
骨肉瘤/Axl/BCL-2/细胞凋亡/预后Key words
osteosarcoma/Axl/BCL-2/apoptosis/prognosis分类
医药卫生引用本文复制引用
蒋念,王雪迪,田锐,谢显彪,赖英荣,彭挺生..骨肉瘤中Axl抑制凋亡及与凋亡蛋白的相关性[J].临床与实验病理学杂志,2017,33(5):490-496,7.基金项目
国家自然科学基金(81302348) （81302348）
