Figová K, Hraběta J, Eckschlager T
Department of Paediatric Haematology and Oncology, Charles University in Prague - Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
Folia Biol (Praha). 2013;59(2):68-75.
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.
溶瘤病毒感染肿瘤细胞、在其中复制并使其裂解，但不会损伤正常细胞。其中一种溶瘤病毒是天然存在的具有复制能力的呼肠孤病毒（RV），它优先杀死具有激活的Ras信号通路的肿瘤细胞。本研究的目的是在缺氧条件下体外研究RV对脑肿瘤衍生细胞的影响，因为缺氧会导致对放疗和化疗产生抗性。本研究表明，RV优先在肿瘤细胞中复制，并且该病毒能够克服细胞对缺氧的适应性，感染并杀死缺氧的肿瘤细胞。RV既能在缺氧的肿瘤微环境中复制，又能引起细胞病变效应，随后诱导细胞死亡。我们发现，很大一部分细胞在缺氧（1%氧气）状态下通过非半胱天冬酶依赖性机制被杀死。此外，我们了解到RV在缺氧条件下诱导的细胞死亡不是由自噬引起的。
