Efficacy of HCC treatment with Proteasome Inhibitor Bortezomib is increased by Oncolytic Virotherapy mediated downregulation of Mcl-1 and Bip

Virotherapy using conditionally replicating adenoviral vectors provides a challenging tool for the tumor treatment. The proteasome inhibitor Bortezomib has been established as anti-cancer agent but potential interference with virotherapy if applied in combination is unkown. Therefore we investigated cytolytic efficacy of either single or combined treaments of hTERT-Ad virotherapy (MOI 25) and/or Bortezomib treatment (10 nM) in Huh-7 HCC cells. Bortezomib killed cells by ER-stress induced apoptosis as shown by Caspase-3 activation and increase of UPR-markers such as CHOP and BIP. Apoptosis was confirmed by downre…