title: Therapeutic enhancement of vascular-targeted photodynamic therapy by inhibiting proteasomal function.
abstract: Vascular-targeted photodynamic therapy (vPDT) is a novel vascular targeting modality based on site-directed delivery of a photosensitizer to tumor vasculature, which induces reactive oxygen species (ROS)-mediated vascular effects upon light activation. To enhance the therapeutic outcome of vPDT, we combined proteasomal inhibitor bortezomib and vPDT using photosensitizer verteporfin in the present study. We found that bortezomib in combination with verteporfin-PDT induced more accumulation of ubiquitinated proteins and apoptosis in endothelial cells than each individual treatment. The combination therapy also enhanced vPDT-induced inhibition in tumor growth. These results indicate that bortezomib can be used together with verteporfin-PDT for enhanced treatment outcome.
authors.affiliation: Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA 19104, USA.
authors.forename: Zhuzhu
authors.initials: Z
authors.lastname: Li
authors.forename: Priyanka
authors.initials: P
authors.lastname: Agharkar
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004357:Drug Synergism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D011166:Porphyrins / Q000008:administration & dosage / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014183:Transplantation, Heterologous; D054875:Ubiquitination / Q000187:drug effects; D000077362:Verteporfin
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; D061988:Proteasome Inhibitors; D017382:Reactive Oxygen Species; D000077362:Verteporfin; D046988:Proteasome Endopeptidase Complex
keywords: Apoptosis; Bortezomib; Combination therapy; Reactive oxygen species (ROS); Ubiquitination; Vascular-targeted photodynamic therapy (vPDT); Verteporfin