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https://doi.org/10.1515/acph-2016-0031

PF573,228 inhibits vascular tumor cell growth, migration as well as angiogenesis, induces apoptosis and abrogates PRAS40 and S6RP phosphorylation

PEACE MABETA ; Angiogenesis Laboratory, Department of Anatomy and Physiology, University of Pretoria, Private Bag X04, Tshwane, 0110, South Africa


Puni tekst: engleski pdf 2.140 Kb

str. 399-410

preuzimanja: 525

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Sažetak

PF573,228 is a compound that targets focal adhesion kinase (FAK), a non-receptor protein kinase, which is over-expressed in various tumors. The aim of this study was to evaluate the effects of PF573,228 on the cells derived from mouse vascular tumors, namely, endothelioma cells.
The treatment of endothelioma cells with PF573,228 reduced their growth with an IC50 of approximately 4.6 µmol L–1and inhibited cell migration with an IC50 of about 0.01 µmol L–1. Microscopic studies revealed morphological attributes of apoptosis. These observations were confirmed by ELISA, which showed increased caspase-3 activity. PF573,228 also inhibited angiogenesis in a dose-dependent manner, with an IC50 of approximately 3.7 µmol L–1 and abrogated the phosphorylation of cell survival proteins, proline-rich Akt substrate (PRAS40) and S6 ribosomal protein (S6RP). Array data further revealed that PF573,228 induced caspase-3 activation, thus promoting apoptosis. Since all the processes inhibited by PF573,228 provide important support to tumor survival and progression, it may have a potential role in the treatment of vascular tumors.

Ključne riječi

PF573,228; focal adhesion kinase; endothelioma; apoptosis; angiogenesis

Hrčak ID:

154688

URI

https://hrcak.srce.hr/154688

Datum izdavanja:

30.9.2016.

Posjeta: 1.032 *