天津医药

天津医药 ›› 2020, Vol. 48 ›› Issue (11): 1050-1054.doi: 10.11958/20200658

• 实验研究 • 上一篇    下一篇

帕比司他抑制卵巢癌裸鼠移植瘤上皮-间质转化和生长机制探讨

秦杰1，柴晓菲2，李向龙3   

  1. 1郑州，河南省直属机关第一门诊部病理科（邮编450000）；2河南省肿瘤医院病理科；3郑州市第七人民医院病理科
  • 收稿日期:2020-03-25 修回日期:2020-08-10 出版日期:2020-11-15 发布日期:2020-11-15

Study on the mechanism of pabitastat inhibiting the epithelial-mesenchymal transition and growth in ovarian cancer xenografts of nude mice

QIN Jie1, CHAI Xiao-fei2, LI Xiang-long3   

  1. 1 Department of Pathology, the First Outpatient Department of the Organs Directly under Henan Province, Zhengzhou 450000, China; 2 Department of Pathology, Henan Tumor Hospital; 3 Department of Pathology, Zhengzhou 7th People’s Hospital
  • Received:2020-03-25 Revised:2020-08-10 Published:2020-11-15 Online:2020-11-15

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摘要： 目的　探究帕比司他（LBH589）对卵巢癌裸鼠移植瘤上皮-间质转化（EMT）、生长及具有PDZ结合域的转录共刺激因子（TAZ）/表皮生长因子受体（EGFR）通路的影响。方法　将造模成功的雌性BALB/c裸鼠50只按随机数字表法分成5组（n=10）：阳性对照组（腹腔注射5 mg/kg贝伐单抗）、模型组（腹腔注射等量生理盐水）以及LBH589低、中、高（腹腔注射10、30及50 nmol/L LBH589）浓度组，干预后每3 d测量各组瘤体积，计算抑瘤率。干预14 d后，采用Western blot法检测各组瘤组织TAZ、EGFR、上皮钙黏附蛋白E（E-Cad）、波形蛋白（Vim）表达。结果　与模型组比较，3 d时阳性对照组、LBH589高浓度组小鼠皮下移植瘤体积减小（P＜0.05），6 d、9 d、12 d时LBH589各浓度组、阳性对照组小鼠皮下移植瘤体积均减小（P＜0.05）；与阳性对照组比较，LBH589低、中浓度组小鼠9 d、12 d时皮下移植瘤体积增大，12 d时抑瘤率降低（P＜0.05）；与LBH589低、中浓度组相比，干预9 d、12 d LBH589高浓度组小鼠皮下移植瘤体积减小，12 d LBH589高浓度组抑瘤率升高（P＜0.05）；与模型组比较，阳性对照组、LBH589各浓度组移植瘤组织中E-Cad蛋白表达升高，Vim、TAZ、EGFR蛋白表达降低（P＜0.05）；与阳性对照组比较，LBH589低、中浓度组移植瘤组织中E-Cad蛋白表达降低，Vim、TAZ、EGFR蛋白表达升高（P＜0.05）；与LBH589低、中浓度组相比，LBH589高浓度组移植瘤组织中E-Cad蛋白表达升高，Vim、TAZ、EGFR蛋白表达降低（P＜0.05）。结论　TAZ/EGFR通路在卵巢癌裸鼠移植瘤生长和EMT中有重要作用，LBH589可能通过抑制TAZ/EGFR通路激活，发挥抑制卵巢癌裸鼠移植瘤生长和EMT的作用。

关键词: 卵巢肿瘤；上皮-间质转化；PDZ结构域；受体, 表皮生长因子；帕比司他；TAZ/EGFR通路

Abstract: Objective To study the effect of pabirstat (LBH589) on the epithelial-mesenchymal transition (EMT), growth and PDZ-binding domain of transcription costimulatory factor (TAZ)/epidermal growth factor receptor (EGFR) pathways of ovarian cancer transplanted tumors in nude mice. Methods Fifty female BALB/c nude mice, successfully modeled, were divided into five groups by the random number table method (n=10): positive control group (5 mg/kg bevacizumab was injected by abdominal cavity), model group (the same amount of saline was injected by abdominal cavity), LBH589 low, medium and high-dose groups (10，30 and 50 nmol/L LBH589 were injected by abdominal cavity). After the intervention, the tumor volumes were measured every 3 days, and the tumor inhibition rates were calculated in each group. Western blot assay was used to verify the expression levels of TAZ, EGFR, E-Cad and Vim in tumor tissues of each group after 14 days of intervention. Results Compared with the model group, after 3 days of intervention, the volumes of subcutaneous tumors were decreased in positive control group and LBH589 high concentration group (P＜0.05). On 6 d, 9 d and 12 d, the volumes of subcutaneous tumors were decreased in the LBH589 low, medium and high concentration groups and the positive control group compared with those of the positive control group (P＜0.05). The volumes of subcutaneous transplanted tumors were increased at 9 d and 12 d in LBH589 low and medium concentration mice, and the tumor inhibition rates were decreased at 12 d (P＜0.05). After 14 days of intervention, the expression levels of E-Cad protein in the transplanted tumor tissues were increased in the positive control group and LBH589 groups compared with those of the model group, and the protein expressions of Vim, TAZ and EGFR were decreased (P＜0.05). Compared with the positive control group, the expressions of E-Cad protein in the transplanted tumor tissues were decreased in LBH589 low and medium concentration groups, and the expressions of Vim, TAZ and EGFR proteins were increased (P＜0.05). Compared with the LBH589 low and medium concentration groups, the E-Cad protein expressions in the transplanted tumor tissues were increased in the LBH589 high concentration group, and the expressions of Vim, TAZ and EGFR proteins were decreased (P＜0.05). Conclusion The TAZ/EGFR pathway plays an important role in the growth and EMT of transplanted ovarian cancer in nude mice. LBH589 may inhibit TAZ/EGFR pathway activation to inhibit the growth and EMT of ovarian cancer in nude mice.

Key words: ovarian neoplasms, epithelial-mesenchymal transition, PDZ domains, receptor,epidermal growth factor, pabistat, TAZ/EGFR pathway