title: Anticancer efficiency of reovirus in normoxia and hypoxia.
abstract: Oncolytic viruses infect, replicate in, and lyse tumour cells but spare the normal ones. One of oncolytic viruses is a naturally occurring replication-competent reovirus (RV), which preferentially kills tumour cells with activated Ras signaling pathways. The aim of this study was to survey effects of RV on brain tumour-derived cells in vitro under hypoxic conditions since hypoxia causes resistance to radio- and chemotherapy. This study demonstrates that RV replicates preferentially in tumour cells and that the virus is able to overcome cellular adaptation to hypoxia and infect and kill hypoxic tumour cells. RV can both replicate in hypoxic tumour microenvironment and cause the cytopathic effect, subsequently inducing cell death. We found that a large proportion of cells are killed in hypoxia (1% O₂) by caspase-independent mechanisms. Furthermore, we learned that the cell death induced by RV in hypoxic conditions is not caused by autophagy.
authors.affiliation: Department of Paediatric Haematology and Oncology, Charles University in Prague - Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
authors.forename: K
authors.initials: K
authors.lastname: Figová
authors.forename: J
authors.initials: J
authors.lastname: Hraběta
authors.forename: T
authors.initials: T
authors.lastname: Eckschlager
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology / Q000821:virology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D051379:Mice; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000187:drug effects / Q000502:physiology*; D010100:Oxygen / Q000494:pharmacology; D012087:Reoviridae / Q000187:drug effects / Q000502:physiology*; D012088:Reoviridae Infections / Q000473:pathology / Q000821:virology
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D053148:Caspase 3; D010100:Oxygen