title: Adenovirus-Mediated Angiotensin II Type 2 Receptor Overexpression Inhibits Tumor Growth of Prostate Cancer In Vivo.
abstract: The renin-angiotensin system (RAS) plays important roles in tumorigenesis and is involved with several hallmarks of cancer. Evidence shows that angiotensin II (AngII) type 1 receptor (AT1R) blockers may be associated with improved outcome in prostate cancer patients. Furthermore, our previous studies indicate that increased expression of Ang II type 2 receptor (AT2R) alone induced apoptosis in human prostate cancer lines, an effect that did not require Ang II. This study aimed to investigate the effects of AT2R on tumor growth in vivo and we hypothesized that AT2R over-expression would inhibit proliferation and induce apoptosis in vivo. Human prostate cancer DU145 xenograft mouse model was used to assess the effect of AT2R on tumor growth in vivo. Mice bearing a palpable tumor were chosen and divided randomly into three treatment groups: AT2R, GFP, and PBS. Then we directly injected into the xenograft tumors of the mice every three days with recombinant adenoviruses encoding AT2R (Ad5-CMV-AT2R-EGFP), EGFP (Ad5-CMV-EGFP) and PBS, respectively. The tumor sizes of the tumor bearing mice were then measured. Immunohistochemical Ki-67 staining and TUNEL assay were performed to examine the inhibitory effect of AT2R on tumor cell proliferation. The results showed that AT2R overexpression can inhibit tumor growth of prostate cancer in vivo by inhibiting proliferation and inducing apoptosis of tumor cells. GADD45A is involved in the AT2R-induced antitumor activity. This suggests that AT2R is a potentially useful gene for prostate gene therapy.
authors.affiliation: 1. School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Li
authors.affiliation: 1. School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Luo
authors.affiliation: 5. Department of Urology, the 421st Hospital of PLA, Guangzhou, Guangdong, China;
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Gu
authors.affiliation: 1. School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Feilong
authors.initials: F
authors.lastname: Jie
authors.affiliation: 6. Department of Clinical Pathology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
authors.forename: Nana
authors.initials: N
authors.lastname: Pei
authors.affiliation: 3. Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, USA;
authors.forename: Andrew
authors.initials: A
authors.lastname: Li
authors.affiliation: 1. School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Xinglu
authors.initials: X
authors.lastname: Chen
authors.affiliation: 1. School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 1. School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Du
authors.affiliation: 1. School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Baihong
authors.initials: B
authors.lastname: Chen
authors.affiliation: 2. Institute of Comparative Medicine and Center of Laboratory Animals, Southern Medical University, Guangzhou, Guangdong, China;
authors.forename: Weiwang
authors.initials: W
authors.lastname: Gu
authors.affiliation: 4. Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida, USA; and.
authors.forename: Colin
authors.initials: C
authors.lastname: Sumners
authors.affiliation: 1. School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Li
keywords: AT2R; Adenovirus; apoptosis.; prostate cancer; tumor growth
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