NDLI: In Vitro Antimetastatic Effect of Phosphatidylinositol 3-Kinase Inhibitor ZSTK474 on Prostate Cancer PC3 Cells

Content Provider	PubMed Central
Author	Zhao, Wennan Guo, Wenzhi Zhou, Qianxiang Ma, Sheng-nan Wang, Ran Qiu, Yuling Jin, Meihua Duan, Hong-quan Kong, Dexin
Copyright Year	2013
Abstract	Tumor metastasis is the main cause of lethality of prostate cancer, because conventional therapies like surgery and hormone treatment rarely work at this stage. Tumor cell migration, invasion and adhesion are necessary processes for metastasis. By providing nutrition and an escape route from the primary site, angiogenesis is also required for tumor metastasis. Phosphatidylinositol 3-kinases (PI3Ks) are well known to play important roles in tumorigenesis as well as metastasis. ZSTK474 is a specific PI3K inhibitor developed for solid tumor therapy. In the present report, antimetastatic activities of ZSTK474 were investigated in vitro by determining the effects on the main metastatic processes. ZSTK474 exhibited inhibitory effects on migration, invasion and adhesive ability of prostate cancer PC3 cells. Furthermore, ZSTK474 inhibited phosphorylation of Akt substrate-Girdin, and the secretion of matrix metalloproteinase (MMP), both of which were reported to be closely involved in migration and invasion. On the other hand, ZSTK474 inhibited the expression of HIF-1α and the secretion of vascular endothelial growth factor (VEGF), suggesting its potential antiangiogenic activity on PC3 cells. Moreover, we demonstrated the antiangiogenesis by determining the effect of ZSTK474-reduced VEGF on tube formation of human umbilical vein endothelial cells (HUVECs). In conclusion, ZSTK474 was demonstrated to have potential in vitro antimetastatic effects on PC3 cells via dual mechanisms: inhibition of metastatic processes including cell migration, invasion and adhesion, and antiangiogenesis via blockade of VEGF secretion.
Related Links	http://dx.doi.org/10.3390/ijms140713577
Ending Page	13591
Page Count	15
Starting Page	13577
File Format	PDF
ISSN	14220067
e-ISSN	14220067
Journal	International Journal of Molecular Sciences
Issue Number	7
Volume Number	14
Language	English
Publisher	Molecular Diversity Preservation International (MDPI)
Publisher Date	2013-06-28
Access Restriction	Open
Rights Holder	Molecular Diversity Preservation International (MDPI)
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Spectroscopy Organic Chemistry Medicine Molecular Biology Physical and Theoretical Chemistry Catalysis Inorganic Chemistry Computer Science Applications

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