The Effect of Chemoradiotherapy with SRC Tyrosine Kinase Inhibitor, PP2 and Temozolomide on Malignant Glioma Cells In Vitro and In Vivo

作者: Keun-Yong Eom , Bong Jun Cho , Eun Jung Choi , Jin-Ho Kim , Eui Kyu Chie

DOI: 10.4143/CRT.2014.320

关键词:

摘要: Purpose We investigated the effect of chemoradiotherapy with PP2 and temozolomide (TMZ) on malignant glioma cells using clonogenic assays in vivo brain tumor model. Materials methods The radiosensitivity U251 T98G was assays. expression E-cadherin, matrix metalloproteinases 2 (MMP2), Ephrin type-A receptor (EphA2), vascular endothelial growth factor (VEGF) measured by Western blotting an accumulation γH2AX foci 6 hours after radiotherapy treatment. migration, invasion, vasculogenic mimicry formation (VMF) evaluated. In orthotopical model cells, injected intraperitoneally or without oral TMZ before, during whole radiotherapy. Bioluminescence images were taken to visualize tumors immunohistochemical staining VEGF, CD31, EphA2, hypoxia-inducible 1a performed. Results increased decreasing survival normal human astrocytes. Chemoradiotherapy resulted foci. induced overexpression E-cadherin suppression MMP2, EphA2. also compromised VMF cells. tumors, decreased volume best, but not statistically significantly compared TMZ. VEGF CD31 suppressed PP2-treated tumors. Conclusion enhances suppresses invasion migration non-significant decrease.

参考文章(24)
Duc M. Le, Arnaud Besson, Darrin K. Fogg, Kyu-Sil Choi, David M. Waisman, Cynthia G. Goodyer, Barry Rewcastle, V. Wee Yong, Exploitation of Astrocytes by Glioma Cells to Facilitate Invasiveness: A Mechanism Involving Matrix Metalloproteinase-2 and the Urokinase-Type Plasminogen Activator–Plasmin Cascade The Journal of Neuroscience. ,vol. 23, pp. 4034- 4043 ,(2003) , 10.1523/JNEUROSCI.23-10-04034.2003
David G. Wilkinson, Multiple roles of eph receptors and ephrins in neural development Nature Reviews Neuroscience. ,vol. 2, pp. 155- 164 ,(2001) , 10.1038/35058515
K. Masui, T. F. Cloughesy, P. S. Mischel, Review: molecular pathology in adult high-grade gliomas: from molecular diagnostics to target therapies. Neuropathology and Applied Neurobiology. ,vol. 38, pp. 271- 291 ,(2012) , 10.1111/J.1365-2990.2011.01238.X
Eric T. Wong, Shiva Gautam, Christopher Malchow, Melody Lun, Edward Pan, Steven Brem, Bevacizumab for Recurrent Glioblastoma Multiforme: A Meta-Analysis Journal of The National Comprehensive Cancer Network. ,vol. 9, pp. 403- 407 ,(2011) , 10.6004/JNCCN.2011.0037
Dominique Stehelin, Donald J. Fujita, Thomas Padgett, Harold E. Varmus, J.Michael Bishop, Detection and enumeration of transformation-defective strains of avian sarcoma virus with molecular hybridization Virology. ,vol. 76, pp. 675- 684 ,(1977) , 10.1016/0042-6822(77)90250-1
Joseph A Hanson, Frank PK Hsu, Arun T Jacob, Daniela A Bota, Daniela Alexandru, Antivascular endothelial growth factor antibody for treatment of glioblastoma multiforme. The Permanente Journal. ,vol. 17, pp. 68- 74 ,(2013) , 10.7812/TPP/13-081
Kyung Min Lee, Eun Jung Choi, In Ah Kim, microRNA-7 increases radiosensitivity of human cancer cells with activated EGFR-associated signaling Radiotherapy and Oncology. ,vol. 101, pp. 171- 176 ,(2011) , 10.1016/J.RADONC.2011.05.050
Na Zhou, Wei-Dong Zhao, Dong-Xin Liu, Yue Liang, Wen-Gang Fang, Bo Li, Yu-Hua Chen, Inactivation of EphA2 promotes tight junction formation and impairs angiogenesis in brain endothelial cells. Microvascular Research. ,vol. 82, pp. 113- 121 ,(2011) , 10.1016/J.MVR.2011.06.005
Chang-Min Park, Myung-Jin Park, Hee-Jin Kwak, Hyung-Chahn Lee, Mi-Suk Kim, Seung-Hoon Lee, In-Chul Park, Chang Hun Rhee, Seok-Il Hong, None, Ionizing Radiation Enhances Matrix Metalloproteinase-2 Secretion and Invasion of Glioma Cells through Src/Epidermal Growth Factor Receptor–Mediated p38/Akt and Phosphatidylinositol 3-Kinase/Akt Signaling Pathways Cancer Research. ,vol. 66, pp. 8511- 8519 ,(2006) , 10.1158/0008-5472.CAN-05-4340
Qiang Ding, Jerry Stewart, Mitchell A. Olman, Michelle R. Klobe, Candece L. Gladson, The Pattern of Enhancement of Src Kinase Activity on Platelet-derived Growth Factor Stimulation of Glioblastoma Cells Is Affected by the Integrin Engaged Journal of Biological Chemistry. ,vol. 278, pp. 39882- 39891 ,(2003) , 10.1074/JBC.M304685200