J Cancer 2016; 7(2):184-191. doi:10.7150/jca.12841
Adenovirus-Mediated Angiotensin II Type 2 Receptor Overexpression Inhibits Tumor Growth of Prostate Cancer In Vivo
1. School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China
2. Institute of Comparative Medicine and Center of Laboratory Animals, Southern Medical University, Guangzhou, Guangdong, China;
3. Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, USA;
4. Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida, USA; and
5. Department of Urology, the 421st Hospital of PLA, Guangzhou, Guangdong, China;
6. Department of Clinical Pathology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
* These authors contributed equally to this work.
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.
Keywords: AT2R, Adenovirus, prostate cancer, tumor growth, apoptosis.
Li J, Luo J, Gu D, Jie F, Pei N, Li A, Chen X, Zhang Y, Du H, Chen B, Gu W, Sumners C, Li H. Adenovirus-Mediated Angiotensin II Type 2 Receptor Overexpression Inhibits Tumor Growth of Prostate Cancer In Vivo. J Cancer 2016; 7(2):184-191. doi:10.7150/jca.12841. Available from http://www.jcancer.org/v07p0184.htm