Cargando…

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

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 pri...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhao, Wennan, Guo, Wenzhi, Zhou, Qianxiang, Ma, Sheng-Nan, Wang, Ran, Qiu, Yuling, Jin, Meihua, Duan, Hong-Quan, Kong, Dexin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742204/
https://www.ncbi.nlm.nih.gov/pubmed/23812078
http://dx.doi.org/10.3390/ijms140713577
_version_ 1782280333070172160
author Zhao, Wennan
Guo, Wenzhi
Zhou, Qianxiang
Ma, Sheng-Nan
Wang, Ran
Qiu, Yuling
Jin, Meihua
Duan, Hong-Quan
Kong, Dexin
author_facet Zhao, Wennan
Guo, Wenzhi
Zhou, Qianxiang
Ma, Sheng-Nan
Wang, Ran
Qiu, Yuling
Jin, Meihua
Duan, Hong-Quan
Kong, Dexin
author_sort Zhao, Wennan
collection PubMed
description 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.
format Online
Article
Text
id pubmed-3742204
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Molecular Diversity Preservation International (MDPI)
record_format MEDLINE/PubMed
spelling pubmed-37422042013-08-13 In Vitro Antimetastatic Effect of Phosphatidylinositol 3-Kinase Inhibitor ZSTK474 on Prostate Cancer PC3 Cells Zhao, Wennan Guo, Wenzhi Zhou, Qianxiang Ma, Sheng-Nan Wang, Ran Qiu, Yuling Jin, Meihua Duan, Hong-Quan Kong, Dexin Int J Mol Sci Article 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. Molecular Diversity Preservation International (MDPI) 2013-06-28 /pmc/articles/PMC3742204/ /pubmed/23812078 http://dx.doi.org/10.3390/ijms140713577 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland http://creativecommons.org/licenses/by/3.0 This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Zhao, Wennan
Guo, Wenzhi
Zhou, Qianxiang
Ma, Sheng-Nan
Wang, Ran
Qiu, Yuling
Jin, Meihua
Duan, Hong-Quan
Kong, Dexin
In Vitro Antimetastatic Effect of Phosphatidylinositol 3-Kinase Inhibitor ZSTK474 on Prostate Cancer PC3 Cells
title In Vitro Antimetastatic Effect of Phosphatidylinositol 3-Kinase Inhibitor ZSTK474 on Prostate Cancer PC3 Cells
title_full In Vitro Antimetastatic Effect of Phosphatidylinositol 3-Kinase Inhibitor ZSTK474 on Prostate Cancer PC3 Cells
title_fullStr In Vitro Antimetastatic Effect of Phosphatidylinositol 3-Kinase Inhibitor ZSTK474 on Prostate Cancer PC3 Cells
title_full_unstemmed In Vitro Antimetastatic Effect of Phosphatidylinositol 3-Kinase Inhibitor ZSTK474 on Prostate Cancer PC3 Cells
title_short In Vitro Antimetastatic Effect of Phosphatidylinositol 3-Kinase Inhibitor ZSTK474 on Prostate Cancer PC3 Cells
title_sort in vitro antimetastatic effect of phosphatidylinositol 3-kinase inhibitor zstk474 on prostate cancer pc3 cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742204/
https://www.ncbi.nlm.nih.gov/pubmed/23812078
http://dx.doi.org/10.3390/ijms140713577
work_keys_str_mv AT zhaowennan invitroantimetastaticeffectofphosphatidylinositol3kinaseinhibitorzstk474onprostatecancerpc3cells
AT guowenzhi invitroantimetastaticeffectofphosphatidylinositol3kinaseinhibitorzstk474onprostatecancerpc3cells
AT zhouqianxiang invitroantimetastaticeffectofphosphatidylinositol3kinaseinhibitorzstk474onprostatecancerpc3cells
AT mashengnan invitroantimetastaticeffectofphosphatidylinositol3kinaseinhibitorzstk474onprostatecancerpc3cells
AT wangran invitroantimetastaticeffectofphosphatidylinositol3kinaseinhibitorzstk474onprostatecancerpc3cells
AT qiuyuling invitroantimetastaticeffectofphosphatidylinositol3kinaseinhibitorzstk474onprostatecancerpc3cells
AT jinmeihua invitroantimetastaticeffectofphosphatidylinositol3kinaseinhibitorzstk474onprostatecancerpc3cells
AT duanhongquan invitroantimetastaticeffectofphosphatidylinositol3kinaseinhibitorzstk474onprostatecancerpc3cells
AT kongdexin invitroantimetastaticeffectofphosphatidylinositol3kinaseinhibitorzstk474onprostatecancerpc3cells