title: Viability reduction and Rac1 gene downregulation of heterogeneous ex-vivo glioma acute slice infected by the oncolytic Newcastle disease virus strain V4UPM.
abstract: Oncolytic viruses have been extensively evaluated for anticancer therapy because this virus preferentially infects cancer cells without interfering with normal cells. Newcastle Disease Virus (NDV) is an avian virus and one of the intensively studied oncolytic viruses affecting many types of cancer including glioma. Nevertheless, the capability of NDV infection on heterogeneous glioma tissue in a cerebrospinal fluid atmosphere has never been reported. Recently, Rac1 is reported to be required for efficient NDV replication in human cancer cells and established a link between tumourigenesis and sensitivity to NDV. Rac1 is a member of the Rho GTPases involved in the regulation of the cell migration and cell-cycle progression. Rac1 knockdown leads to significant inhibition of viral replication. In this work, we demonstrated that NDV treatment led to significant reduction of tumour tissue viability of freshly isolated heterogeneous human brain tumour slice, known as an ex vivo glioma acute slice (EGAS). Analysis of gene expression indicated that reduced tissue viability was associated with downregulation of Rac1. However, the viability reduction was not persistent. We conclude that NDV treatment induced EGAS viability suppression, but subsequent downregulation of Rac1 gene may reduce the NDV replication and lead to regrowth of EGAS tissue.
authors.affiliation: Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.
authors.forename: Zulkifli
authors.initials: Z
authors.lastname: Mustafa
authors.forename: Hilda Shazana
authors.initials: HS
authors.lastname: Shamsuddin
authors.forename: Aini
authors.initials: A
authors.lastname: Ideris
authors.forename: Rohaya
authors.initials: R
authors.lastname: Ibrahim
authors.forename: Hasnan
authors.initials: H
authors.lastname: Jaafar
authors.forename: Abdul Manaf
authors.initials: AM
authors.lastname: Ali
authors.forename: Jafri Malin
authors.initials: JM
authors.lastname: Abdullah
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000628:therapy*; D006801:Humans; D009522:Newcastle disease virus / Q000235:genetics; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D020830:rac1 GTP-Binding Protein / Q000096:biosynthesis*
chemical_list: D020830:rac1 GTP-Binding Protein