Adenovirus-Mediated Angiotensin II Type 2 Receptor Overexpression Inhibits Tumor Growth of Prostate Cancer In Vivo.
Adenovirus-Mediated Angiotensin II Type 2 Receptor Overexpression Inhibits Tumor Growth of Prostate Cancer In Vivo.
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腺病毒介导的血管紧张素 II 2 型受体过表达抑制体内前列腺癌的肿瘤生长
DOI：
10.7150/jca.12841
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发表时间：
2016
影响因子：
3.9
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
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
肾素-血管紧张素系统（RAS）在肿瘤发生中起着重要作用，并与癌症的几个特征有关。有证据表明血管紧张素II (AngII) 1型受体（AT1R）阻滞剂可能与前列腺癌患者预后改善有关。此外，我们之前的研究表明，单独增加Ang II 2型受体（AT2R）的表达可诱导人前列腺癌细胞细胞凋亡，而这种作用不需要Ang II。本研究旨在探讨AT2R对体内肿瘤生长的影响，我们假设AT2R过表达会抑制体内肿瘤的增殖并诱导细胞凋亡。采用人前列腺癌DU145异种移植小鼠模型，在体内评价AT2R对肿瘤生长的影响。选择可触及肿瘤的小鼠，随机分为三个治疗组：AT2R、GFP和PBS。然后每隔3天将编码AT2R （Ad5-CMV-AT2R-EGFP）、EGFP （Ad5-CMV-EGFP）和PBS的重组腺病毒直接注射到小鼠的异种移植瘤中。然后测量荷瘤小鼠的肿瘤大小。免疫组化Ki-67染色及TUNEL法检测AT2R对肿瘤细胞增殖的抑制作用。结果表明，AT2R过表达在体内可通过抑制肿瘤细胞增殖和诱导肿瘤细胞凋亡来抑制前列腺癌的肿瘤生长。GADD45A参与at2r诱导的抗肿瘤活性。这表明AT2R是前列腺基因治疗的潜在有用基因。
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.