Knockdown of vascular endothelial cell growth factor expression sensitizes U251 glioma cells to liposomal paclitaxel and radiation treatment in vitro

Yu,Yang; Feng,Jianguo; Zong,Xiangyun; Yang,Hongjian; Zou,Dehong; He,Xiangming

doi:10.3892/etm.2011.379

Knockdown of vascular endothelial cell growth factor expression sensitizes U251 glioma cells to liposomal paclitaxel and radiation treatment in vitro

Authors:
- Yang Yu
- Jianguo Feng
- Xiangyun Zong
- Hongjian Yang
- Dehong Zou
- Xiangming He
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Affiliations: Department of Surgical Oncology, Zhejiang Cancer Hospital, Hangzhou, P.R. China
Published online on: November 11, 2011 https://doi.org/10.3892/etm.2011.379
Pages: 181-186

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Abstract

Glioblastoma is the most aggressive malignancy of the human brain, accounting for 40% of all primary malignant brain tumors. However, there is no effective treatment for this disease. This study was designed to develop anti-vascular endothelial growth factor (VEGF) as a novel adjuvant therapy for glioblastoma. A VEGF shRNA vector was constructed to silence VEGF expression in U251 glioma cells and these cells were treated with various concentrations of liposomal paclitaxel, 6 Gy radiation or liposomal paclitaxel plus radiation. The data demonstrated that the VEGF shRNA vector significantly knocked down VEGF expression, which synergistically sensitized U251 glioma cells to liposomal paclitaxel, radiation or liposomal paclitaxel plus radiation treatment in terms of cell viability, apoptosis, colony formation and morphological changes. Future studies are required to evaluate these effects in vivo.

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1.	A JemalT MurrayE WardCancer statisticsCA Cancer J Clin5510302005
2.	A BehinK Hoang-XuanAF CarpentierPrimary brain tumours in adultsLancet361323331200310.1016/S0140-6736(03)12328-812559880
3.	MA MeyerMalignant gliomas in adultsN Engl J Med35918502007
4.	FB FurnariT FentonRM BachooMalignant astrocytic glioma: genetics, biology, and paths to treatmentGenes Dev2126832710200710.1101/gad.159670717974913
5.	PC De Witt HamerSmall molecule kinase inhibitors in glioblastoma: a systematic review of clinical studiesNeuro Oncol12304316201020167819
6.	HW LoEGFR-targeted therapy in malignant glioma: novel aspects and mechanisms of drug resistanceCurr Mol Pharmacol33752201010.2174/187446721100301003720030624
7.	M MacheinLS de MiguelAngiogenesis in gliomasRecent Results Cancer Res171193215200910.1007/978-3-540-31206-2_12
8.	RK JainE di TomasoDG DudaAngiogenesis in brain tumoursNat Rev Neurosci8610622200710.1038/nrn2175
9.	MI LinWC SessaAntiangiogenic therapy: creating a unique ‘window’ of opportunityCancer Cell65295312004
10.	HM SaidC HagemannA StaabExpression patterns of the hypoxia-related genes osteopontin, CA9, erythropoietin, VEGF and HIF-1alpha in human glioma in vitro and in vivoRadiother Oncol83398405200710.1016/j.radonc.2007.05.00317524506
11.	V DamianoD MelisiC BiancoCooperative antitumor effect of multitargeted kinase inhibitor ZD6474 and ionizing radiation in glioblastomaClin Cancer Res1156395644200510.1158/1078-0432.CCR-05-017416061883
12.	A AbdollahiKE LipsonA SckellCombined therapy with direct and indirect angiogenesis inhibition results in enhanced anti-angiogenic and antitumor effectsCancer Res6388908898200314695206
13.	WS KamounCD LeyCT FarrarEdema control by cediranib, a vascular endothelial growth factor receptor-targeted kinase inhibitor, prolongs survival despite persistent brain tumor growth in miceJ Clin Oncol2725422552200910.1200/JCO.2008.19.9356
14.	G TabatabaiB FrankA WickSynergistic antiglioma activity of radiotherapy and enzastaurinAnn Neurol61153161200710.1002/ana.2105717212356
15.	PR WachsbergerR BurdC CardiVEGF trap in combination with radiotherapy improves tumor control in u87 glioblastomaInt J Radiat Oncol Biol Phys6715261537200710.1016/j.ijrobp.2006.11.01117234361
16.	F WinklerSV KozinRT TongKinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinasesCancer Cell65535632004
17.	KE HovingaLJ StalpersC van BreeRadiation-enhanced vascular endothelial growth factor (VEGF) secretion in glioblastoma multiforme cell lines - a clue to radioresistance?J Neurooncol7499103200510.1007/s11060-004-4204-716193379
18.	G FountzilasG KarkavelasA Kalogera-FountzilaPost-operative combined radiation and chemotherapy with temozolomide and irinotecan in patients with high-grade astrocytic tumors. A phase II study with biomarker evaluationAnticancer Res2646754686200617214326
19.	S KesariD SchiffJW HensonPhase II study of temozolomide, thalidomide, and celecoxib for newly diagnosed glioblastoma in adultsNeuro Oncol10300308200810.1215/15228517-2008-00518403492
20.	Y MatsumuraA MaedaA new concept for macromolecular therapies in cancer chemotherapy: mechanisms of tumortropic accumulation of proteins and the antitumor agents smancsCancer Res466387639219862946403
21.	KJ HarringtonS MohammadtaghiPS UsterEffective targeting of solid tumors in patients with locally advanced cancers by radiolabeled pegylated liposomesClin Cancer Res7243254200111234875
22.	CO NobleDB KirpotinME HayesDevelopment of ligand targeted liposomes for cancer therapyExpert Opin Ther Targets8335353200410.1517/14728222.8.4.33515268628
23.	H AokiK KakinumaK MoritaTherapeutic efficacy of targeting chemotherapy using local hyperthermia and thermosensitive liposome: evaluation of drug distribution in a rat glioma modelInt J Hypertherm20595605200510.1080/0265673041000170318615370816
24.	C MamotJB NguyenM PourdehnadExtensive distribution of liposomes in rodent brains and brain tumors following convection-enhanced deliveryJ Neurooncol6819200410.1023/B:NEON.0000024743.56415.4b15174514