SRC family kinase inhibitor SU6656 enhances antiangiogenic effect of irradiation

International Journal of Radiation Oncology, Biology, Physics
Kyle C CuneoDennis E Hallahan

Abstract

Src family kinases (SFK) have been identified as molecular targets. SU6656 is a small-molecle indolinone that specifically inhibits this family of kinases. Human umbilical vein endothelial cells were used to study the effects of SFK inhibition. Western blot analysis was performed to determine the effect of SFK inhibition on the PI3K/Akt pathway and caspase cleavage. Apoptosis was studied by propidium iodide staining of nuclei. Angiogenesis was examined using capillary tubule formation in Matrigel. Tumor response was further studied in vivo using Lewis lung carcinoma cells implanted into the dorsal skin fold of mice in the window model and in the hind limb in the tumor volume model. Clonogenic survival of endothelial cells was decreased after the combined therapy of SU6656 and radiation compared with radiotherapy alone. Furthermore, SFK inhibition by SU6656 attenuated radiation-induced Akt phosphorylation and increased radiation-induced apoptosis and vascular endothelium destruction. In vivo, SU6656 administered before irradiation significantly enhanced radiation-induced destruction of blood vessels within the tumor windows and enhanced tumor growth delay when administered during fractionated irradiation. This study demonstrates...Continue Reading

References

Jan 1, 1975·Annals of Internal Medicine·J Folkman
Jan 1, 1997·Annual Review of Cell and Developmental Biology·S M Thomas, J S Brugge
Nov 14, 2000·Molecular and Cellular Biology·R A BlakeS A Courtneidge
Dec 21, 2000·Trends in Pharmacological Sciences·M SusvaJ Green
Jun 5, 2001·Nature Reviews. Molecular Cell Biology·G S Martin

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Citations

Sep 1, 2007·Angiogenesis·Ling GengDennis E Hallahan
Jul 24, 2010·Journal of Oncology·Jessie ZhongGeraldine M O'Neill
May 23, 2012·Expert Opinion on Investigational Drugs·Tadeusz Robak, Ewa Robak
May 7, 2011·Cancer Treatment Reviews·Renaud MazeronEric Deutsch
Oct 16, 2010·Cancer Letters·Manmeet S AhluwaliaCandece L Gladson
May 14, 2010·Reproductive Biomedicine Online·Xiu-Zhen Zhang
Sep 27, 2012·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Uma RajuK Kian Ang
Jun 6, 2015·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Keun-Yong EomIn Ah Kim
Jun 21, 2008·Cell Death and Differentiation·E M YazlovitskayaD E Hallahan
May 14, 2009·Journal of Neuro-oncology·John de Groot, Vanessa Milano
Jun 18, 2020·Cancers·Claudia CirottiDaniela Barilà
May 19, 2007·Cancer Research·Kyle C CuneoChristopher D Willey
Jun 23, 2021·Journal of Experimental & Clinical Cancer Research : CR·Irma TelarovicMartin Pruschy

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