Cancer Therapy: Preclinical Bortezomib-Induced Unfolded Protein Response Increases Oncolytic HSV-1 Replication Resulting in Synergistic Antitumor Effects

  • Ji YoungYoo, Brian S.Hurwitz, +13 authors Balveen Kaur
  • Published 2014

Abstract

Background:Bortezomib is an FDA-approved proteasome inhibitor, andoncolytic herpes simplex virus1 (oHSV) is a promising therapeutic approach for cancer. We tested the impact of combining bortezomib with oHSV for antitumor efficacy. Experimental Design: The synergistic interaction between oHSV and bortezomib was calculated using Chou–Talalay analysis. Viral replication was evaluated using plaque assay and immune fluorescence. Western blot assays were used to evaluate induction of estrogen receptor (ER) stress and unfolded protein response (UPR). Inhibitors targeting Hsp90 were utilized to investigate the mechanism of cell killing. Antitumor efficacy in vivowas evaluated using subcutaneous and intracranial tumor xenografts of glioma and head and neck cancer. Survival was analyzed by Kaplan–Meier curves and two-sided log-rank

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Cite this paper

@inproceedings{YoungYoo2014CancerTP, title={Cancer Therapy: Preclinical Bortezomib-Induced Unfolded Protein Response Increases Oncolytic HSV-1 Replication Resulting in Synergistic Antitumor Effects}, author={Ji YoungYoo and Brian S.Hurwitz and ChelseaBolyard and Jun-GeYu and JianyingZhang and KaruppaiyahSelvendiran and Kellie S. Rath and Shun He and Zachary J. Bailey and David W Eaves and Timothy P. Cripe and Deborah S. Parris and Michael A . Caligiuri and Jianhua Yu and Matthew O. Old and Balveen Kaur}, year={2014} }