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Antiangiogenic Agent Nintedanib (BIBF 1120) Effectiveness in vitro and in vivo Against Prostate Cancer
Author(s) -
Silva Raquel Frenedoso,
Raina Komal,
Kumar Dileep,
Dhar Deepanshi,
Cag Valéria Helena Alves,
Agarwal Chapla,
Agarwal Rajesh
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb30
Subject(s) - nintedanib , tramp , prostate cancer , angiogenesis , stromal cell , medicine , prostate , proliferation index , in vivo , angiogenesis inhibitor , urology , cancer research , hyperplasia , pathology , cancer , immunohistochemistry , biology , lung , idiopathic pulmonary fibrosis , microbiology and biotechnology
Nintedanib is a compound capable of inhibiting angiogenesis, preventing cell proliferation and decreasing tumor volume. This study was aimed at evaluating Nintedanib efficacy in prostate cancer (PCa) cell lines, besides morphological and molecular features in PCa development in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. PC3 and LNCaP cells were treated with either DMSO alone or Nintedanib (2.5, 5.0, 10 or 25 μM) in DMSO and assessed for viability and clonogenicity. Furthermore, male TRAMP mice were divided into control (Tween 20 (10%)) and treatment groups receiving Nintedanib (10mg/Kg/day) for 4 weeks. The animals were treated either from 8 to 12 weeks of age and euthanized both at 12 and 22 weeks of age or treated from 12 to 16 weeks of age and euthanized both at 16 and 22 weeks of age. At the end of the study, prostate ventral lobes were collected for structural, immunohistochemical and protein analyses for AR, ERα, FGF‐2, VEGF, microvessel density and proliferative index. Nintedanib treatment effectively decreased the total cell number and the survival of colonies. Morphological evaluation of TRAMP mouse prostate showed reduced number of lesions and the stromal hypertrophy after Nintedanib exposure. The treatment also caused a significant reduction in AR levels in epithelial cells and FGF‐2 in both prostatic stromal and epithelial cells. This was accompanied by a decrease in the microvessel density and VEGF immunolocalization. Furthermore, the proliferative index was also diminished by drug treatment. Nintedanib is effective against PCa in vitro and in vivo , due to the delayed neoplastic development in the glandular microenvironment and downregulation of multiple pathways involved in prostate tumorigenesis. Support or Funding Information Funding: FAPESP 2013/26677‐7 Ethics Committee 3285‐1