Targeting Gene-ViroTherapy for prostate cancer by DD3-driven oncolytic virus-harboring interleukin-24 gene.
Prostate cancer (PCa) is the second leading cause of cancer-related deaths in Western male population. Previous studies have demonstrated that differential display code 3 (DD3 or DD3(PCA3)) is one of the most PCa-specific genes; therefore, it has been used as a clinical diagnostic marker for PCa. In this study, we constructed an oncolytic adenovirus Ad.DD3-E1A by using the minimal DD3 promoter to replace the native viral promoter of E1A gene. In addition, Ad.DD3-E1A was armed with therapeutic gene IL-24 to enhance its antitumor activity. The resulting adenovirus, Ad.DD3-E1A-IL-24, demonstrated PCa specificity and excellent antitumor effect. Further analyses on its antitumor mechanism revealed that it has the capacity to induce apoptosis in PCa cells and inhibit angiogenesis. These results suggest that Ad.DD3-E1A-IL-24 is a promising antitumor agent that may be able to be used in the future as a treatment for PCa.
Fan
Jun Kai
JK
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Wei
Na
N
Ding
Miao
M
Gu
Jin Fa
JF
Liu
Xin Ran
XR
Li
Bing Hua
BH
Qi
Rong
R
Huang
Wei Dan
WD
Li
Yu Hua
YH
Xiong
Xiao Quan
XQ
Wang
Jian
J
Li
Run Sheng
RS
Liu
Xin Yuan
XY
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics*; D017209:Apoptosis; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D017931:DNA Primers; D015316:Genetic Therapy; D006801:Humans; D007378:Interleukins / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D000099180:Interleukin-24
D000951:Antigens, Neoplasm; D017931:DNA Primers; D007378:Interleukins; D000099180:Interleukin-24; C479341:prostate cancer antigen 3, human