In:
Current Cancer Drug Targets, Bentham Science Publishers Ltd., Vol. 19, No. 4 ( 2019-03-21), p. 321-329
Abstract:
The lethality of prostate cancer is mainly due to metastasis. Inhibition of
metastasis is expected to be a promising approach for prostate cancer therapy. Phosphatidylinositol 3-kinase (PI3K)/Akt pathway is reported to be closely involved in cell growth, migration, etc. Objective: The study investigated the antimetastatic activities of pan-PI3K inhibitor ZSTK474 on
DU145 cells. Methods: 1. The In vitro effect of ZSTK474 on the migration, invasion and adhesion of DU145
cells was determined with Transwell migration assay and wound healing assay, Tranwell invasion assay and adhesion assay, respectively. 2. In vitro effect of ZSTK474 on the signal proteins in
DU145 cells was determined with Western blot analysis and ELISA. 3. Moreover, the In vivo antimetastatic effect of ZSTK474 was evaluated with MicroCT and histology analysis. Results: ZSTK474 potently attenuated the capability of migration, invasion and adhesion of DU145
cells, negatively regulated Girdin, Integrinβ1 and matrix metalloproteinases (MMPs). In addition, the expression of hypoxia-inducible factor-1 & #945; (HIF-1 & #945;) and vascular endothelial growth factor
(VEGF), which are known to be related to angiogenesis and metastasis, was also inhibited. Oral administration of ZSTK474 (200 mg/kg) ameliorated in vivo bone metastasis of DU145 cells, with
improved bone structure and bone mineral density (BMD). Tissue staining indicated a reduction in metastatic DU145 cells and osteoclasts in the bones of ZSTK474-treated mice, compared with the
non-treated group. Conclusion: Our result demonstrated the antimetastatic activity of ZSTK474 on prostate cancer
DU145 cells, suggesting the potential application in prostate cancer patients.
Type of Medium:
Online Resource
ISSN:
1568-0096
DOI:
10.2174/1568009618666180911101310
Language:
English
Publisher:
Bentham Science Publishers Ltd.
Publication Date:
2019
SSG:
15,3
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