GOLPH2-regulated oncolytic adenovirus, GD55, exerts strong killing effect on human prostate cancer stem-like cells in vitro and in vivo  

作　　者：Chang YING Bo-duan XIAO Yun QIN Bin-rong WANG Xin-yuan LIU Ru-wei WANG Ling FANG Hui YAN Xiu-meiZHOU Yi-gang WANG 

机构地区：[1]Xinyuan Institute of Medicine and Biotechnology, College of Life Sciences Zhejiang Sci-Tech University, Hangzhou 310018, China [2]Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China [3]Zhejiang Conba Pharmaceutical Co., Ltd, Hangzhou 310018, China [4]Zhejiang Academy of Medical Sciences, Hangzhou 310013, China

出　　处：《Acta Pharmacologica Sinica》2018年第3期405-414,共10页中国药理学报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China （No 81272687 and 81573000）, Zhejiang Provincial Natural Science Foundation of China （No LY16H160056）, Zhejiang Province Health Department （No 2014RCA022）, Grant for 521 Talent Project of ZSTU and Aca- demician Workstation of Zhejiang Province.

摘　　要：GOLPH2 （also called GP73） is a Golgi glycoprotein, which has been identified as a novel tumor marker upregulated in various cancers, including prostate cancer （PCa）. GD55 is a novel GOLPH2-regulated oncolytic adenovirus that exhibits a strong killing effect on hepatoma cells. Here, we investigate the antitumor effect of GD55 on prostate cancer stem cell （CSC）-Iike cells in vitro and in vivo. Prostate CSC-like sphere cells were acquired and enriched by culturing DU145, LNCap or P3 prostate cancer cells in suspension. The prostate CSC-like sphere cells were capable of self-renewal, differentiation and quiescence, displaying tumorigenic feature and chemo-resistance to 5-FU, doxorubicin and DDP. Treatment with GD55 （1, 5, 10 MOI） dose-dependently suppressed the viability of DU145 sphere cells, which was a more pronounced compared to its cytotoxic action on the parental DU145 cells. In a mouse xenograft prostate CSC-like model, intratumoral injection of GD55 markedly suppressed the growth rate of xenograft tumors and induced higher levels of cell death and necrosis within the tumor tissues. Our results demonstrate that GD55 infection exerts strong anticancer effects on prostate CSC-like cells in vitro and in vivo, and has a potential to be used in the clinical therapy of PCa.GOLPH2 （also called GP73） is a Golgi glycoprotein, which has been identified as a novel tumor marker upregulated in various cancers, including prostate cancer （PCa）. GD55 is a novel GOLPH2-regulated oncolytic adenovirus that exhibits a strong killing effect on hepatoma cells. Here, we investigate the antitumor effect of GD55 on prostate cancer stem cell （CSC）-Iike cells in vitro and in vivo. Prostate CSC-like sphere cells were acquired and enriched by culturing DU145, LNCap or P3 prostate cancer cells in suspension. The prostate CSC-like sphere cells were capable of self-renewal, differentiation and quiescence, displaying tumorigenic feature and chemo-resistance to 5-FU, doxorubicin and DDP. Treatment with GD55 （1, 5, 10 MOI） dose-dependently suppressed the viability of DU145 sphere cells, which was a more pronounced compared to its cytotoxic action on the parental DU145 cells. In a mouse xenograft prostate CSC-like model, intratumoral injection of GD55 markedly suppressed the growth rate of xenograft tumors and induced higher levels of cell death and necrosis within the tumor tissues. Our results demonstrate that GD55 infection exerts strong anticancer effects on prostate CSC-like cells in vitro and in vivo, and has a potential to be used in the clinical therapy of PCa.

关 键 词：prostate cancer cancer stem cells GOLPH2 oncolytic adenovirus GD55 antitumor agents cancer targeting genevirotherapy 

分 类 号：S858.316.3[农业科学—临床兽医学] TN929.53[农业科学—兽医学]