{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Cataldi M"],"funding":["National Cancer Institute","NCI NIH HHS"],"pagination":["340-54"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4619123"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["485"],"pubmed_abstract":["Vesicular stomatitis virus (VSV) is an effective oncolytic virus against most human pancreatic ductal adenocarcinoma (PDAC) cell lines. However, some PDAC cell lines are highly resistant to oncolytic VSV-ΔM51 infection. To better understand the mechanism of resistance, we tested a panel of 16 small molecule inhibitors of different cellular signaling pathways, and identified TPCA-1 (IKK-β inhibitor) and ruxolitinib (JAK1/2 inhibitor), as strong enhancers of VSV-ΔM51 replication and virus-mediated oncolysis in all VSV-resistant PDAC cell lines. Both TPCA-1 and ruxolitinib similarly inhibited STAT1 and STAT2 phosphorylation and decreased expression of antiviral genes MxA and OAS. Moreover, an in situ kinase assay provided biochemical evidence that TPCA-1 directly inhibits JAK1 kinase activity"],"journal":["Virology"],"pubmed_title":["Breaking resistance of pancreatic cancer cells to an attenuated vesicular stomatitis virus through a novel activity of IKK inhibitor TPCA-1."],"pmcid":["PMC4619123"],"funding_grant_id":["1R15CA167517-01","R15 CA167517"],"pubmed_authors":["Felt SA","Cataldi M","Shah NR","Grdzelishvili VZ"],"additional_accession":[]},"is_claimable":false,"name":"Breaking resistance of pancreatic cancer cells to an attenuated vesicular stomatitis virus through a novel activity of IKK inhibitor TPCA-1.","description":"Vesicular stomatitis virus (VSV) is an effective oncolytic virus against most human pancreatic ductal adenocarcinoma (PDAC) cell lines. However, some PDAC cell lines are highly resistant to oncolytic VSV-ΔM51 infection. To better understand the mechanism of resistance, we tested a panel of 16 small molecule inhibitors of different cellular signaling pathways, and identified TPCA-1 (IKK-β inhibitor) and ruxolitinib (JAK1/2 inhibitor), as strong enhancers of VSV-ΔM51 replication and virus-mediated oncolysis in all VSV-resistant PDAC cell lines. Both TPCA-1 and ruxolitinib similarly inhibited STAT1 and STAT2 phosphorylation and decreased expression of antiviral genes MxA and OAS. Moreover, an in situ kinase assay provided biochemical evidence that TPCA-1 directly inhibits JAK1 kinase activity","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015 Nov","modification":"2026-04-07T18:12:49.357Z","creation":"2019-03-27T02:00:44Z"},"accession":"S-EPMC4619123","cross_references":{"pubmed":["26331681"],"doi":["10.1016/j.virol.2015.08.003"]}}