Tianjin Medical Journal ›› 2020, Vol. 48 ›› Issue (11): 1050-1054.doi: 10.11958/20200658

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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

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