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X. Song, X. Fan, R. Jia, Y. Zhou, X. Xu, H. Wang, S. Ge; Inhibition of Retinoblastoma in vitro and in vivo With Conditionally Replicating Oncolytic Adenovirus H101. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1693.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the functional effects of oncolytic adenovirus H101 on retinoblastoma in vitro and in vivo.
The expression of Coxsackie-adenovirus receptor (CAR) in the human retinoblastoma cell line HXO-RB44 was determined by reverse transcription polymerase chain reaction (RT-PCR). Retinoblastoma cells were incubated with green fluorescent protein (GFP)-labeled adenovirus (AdGFP) and appropriate multiplicity of infection (MOI) was determined using flow cytometry. Cell viability of HXO-RB44 treated with H101 or AdGFP was measured using a CCK8-based procedure. Viral proliferation was measured through endpoint dilution titration on 293 human embryonic kidney cells and real-time PCR. Cell cycle and apoptosis were analyzed by flow cytometry. NOD-SCID mice bearing retinoblastoma xenografts were treated with intratumoral injection of H101, AdGFP, or phosphate-buffered saline. Tumor volume and survival time were recorded. Immunohistochemistry for adenoviral fiber protein in paraffin-embedded tissue sections of retinoblastoma xenografts was performed to evaluate H101 virus replication in vivo.
HXO-RB44 cells extensively expressed CAR and were sensitive to adenoviral infection. HXO-RB44 cells treated with H101 had dramatically reduced cell viability compared with AdGFP-treated cells (P<0.01). Abundant replication of H101 was observed in HXO-RB44 cells, resulting in G2/M phase arrest, but there was no apoptosis. Tumor-bearing mice treated with H101 had significantly reduced tumor volume (68%) and significantly prolonged survival time (170%) compared with controls (both P<0.01). Immunohistochemical examination revealed widespread replication of H101 within the tumor.
These results suggest that oncolytic adenovirus H101 effectively inhibits retinoblastoma cells in vitro and in vivo, and may be useful for the clinical treatment of retinoblastoma.
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