RRC ID 36054
Author Shen YH, Yang F, Wang H, Cai ZJ, Xu YP, Zhao A, Su Y, Zhang G, Zhu SX.
Title Arg-Gly-Asp (RGD)-Modified E1A/E1B Double Mutant Adenovirus Enhances Antitumor Activity in Prostate Cancer Cells In Vitro and in Mice.
Journal PLoS One
Abstract CAR is a transmembrane protein that is expressed in various epithelial and endothelial cells. CAR mediates adenoviral infection, as well as adenovirus-mediated oncolysis of AxdAdB-3, an E1A/E1B double-restricted oncolytic adenovirus, in prostate cancer cells. This study further assessed the therapeutic efficacy of AxdAdB-3 with Arg-Gly-Asp (RGD)-fiber modification (AxdAdB3-F/RGD), which enables integrin-dependent infection, in prostate cancer. Susceptibility of prostate cancer cells LNCaP, PC3, and DU145 to adenovirus infection was associated with CAR expression. All of the prostate cancer cell lines expressed integrin αvβ3 and αvβ5. AxdAdB-3 was more cytopathic in CAR-positive prostate cancer cells than in CAR-negative cells, whereas AxdAdB3-F/RGD caused potent oncolysis in both CAR-positive and CAR-negative prostate cancer cells. In contrast, AxdAdB3-F/RGD was not cytopathic against normal prostate epithelial cells, RWPE-1. Intratumoral injection of AxdAdB3-F/RGD into CAR-negative prostate cancer cell xenografts in nude mice inhibited tumor growth. The current study demonstrates that E1A/E1B double-restricted oncolytic adenovirus with an RGD-fiber modification enhances infection efficiency and anti-tumor activity in CAR-deficient prostate cancer cells, while sparing normal cells. Future studies will evaluate the therapeutic potential of AxdAdB3-F/RGD in prostate cancer.
Volume 11(1)
Pages e0147173
Published 2016-1-1
DOI 10.1371/journal.pone.0147173
PII PONE-D-15-18311
PMID 26799485
PMC PMC4723068
MeSH Adenoviridae / genetics* Adenovirus E1A Proteins / genetics* Adenovirus E1B Proteins / genetics* Animals Cell Line, Tumor Cytopathogenic Effect, Viral Humans In Vitro Techniques Male Mice Mutation* Oligopeptides / genetics* Prostatic Neoplasms / pathology*
IF 2.74
Times Cited 12
DNA material AxCALacZ (RDB01745) AxCAZ3-F/RGD (RDB02194) AxdAdB-3 (RDB02176) AxdAdB3-F/RGD (RDB03012).