Effects of angiotensin II type 2 receptor overexpression on the growth of hepatocellular carcinoma cells in vitro and in vivo.
Effects of angiotensin II type 2 receptor overexpression on the growth of hepatocellular carcinoma cells in vitro and in vivo.
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DOI：
10.1371/journal.pone.0083754
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Du H;Liang Z;Zhang Y;Jie F;Li J;Fei Y;Huang Z;Pei N;Wang S;Li A;Chen B;Zhang Y;Sumners C;Li M;Li H
越来越多的证据表明肾素-血管紧张素系统（RAS）在肿瘤发生中发挥着重要作用。血管紧张素II（AngII）和血管紧张素1型受体（AT1R）之间的相互作用可能在肝细胞癌（HCC）中发挥关键作用，因此，AT1R阻滞剂和血管紧张素I转换酶（ACE）抑制剂可能在肝癌的治疗中具有治疗潜力。尽管 AT1R 的参与已得到充分探索，但血管紧张素 II 2 型受体 (AT2R) 在 HCC 进展中的作用仍知之甚少。因此，本研究的目的是探讨 AT2R 过表达对体外 HCC 细胞和人类 HCC 小鼠模型的影响。 AT2R 重组腺病毒载体 (Ad-G-AT2R-EGFP) 被转导至 HCC 细胞系和原位肿瘤移植物中。结果表明，高剂量 Ad-G-AT2R-EGFP 诱导转导的 HCC 细胞系中 AT2R 过度表达，产生细胞凋亡。 SMMC7721 细胞中 AT2R 过表达可抑制细胞增殖，通过改变 CDK4 和 cyclinD1 的表达，S 期细胞显着减少，G1 期细胞富集。数据还表明，AT2R 的过度表达通过细胞死亡信号通路导致细胞凋亡，该信号通路依赖于 p38 MAPK、pJNK、caspase-8 和 caspase-3 的激活以及 pp42/44 MAPK (Erk1/2) 的失活。最后，我们证明适度增加 AT2R 表达可以增加 HCC 肿瘤的生长和体内 HCC 细胞的增殖。我们的研究结果表明，AT2R 过表达在体外和体内调节肝细胞癌细胞的增殖，但这种现象的确切机制尚未完全确定。
Increasing evidence suggests that the renin-angiotensin system (RAS) plays an important role in tumorigenesis. The interaction between Angiotensin II (AngII) and angiotensin type 1 receptor (AT1R) may have a pivotal role in hepatocellular carcinoma (HCC) and therefore, AT1R blocker and angiotensin I-converting enzyme (ACE) inhibitors may have therapeutic potential in the treatment of hepatic cancer. Although the involvement of AT1R has been well explored, the role of the angiotensin II Type 2 receptor (AT2R) in HCC progression remains poorly understood. Thus, the aim of this study was to explore the effects of AT2R overexpression on HCC cells in vitro and in mouse models of human HCC. An AT2R recombinant adenoviral vector (Ad-G-AT2R-EGFP) was transduced into HCC cell lines and orthotopic tumor grafts. The results indicate that the high dose of Ad-G-AT2R-EGFP–induced overexpression of AT2R in transduced HCC cell lines produced apoptosis. AT2R overexpression in SMMC7721 cells inhibited cell proliferation with a significant reduction of S-phase cells and an enrichment of G1-phase cells through changing expression of CDK4 and cyclinD1. The data also indicate that overexpression of AT2R led to apoptosis via cell death signaling pathway that is dependent on activation of p38 MAPK, pJNK, caspase-8 and caspase-3 and inactivation of pp42/44 MAPK (Erk1/2). Finally, we demonstrated that moderately increasing AT2R expression could increase the growth of HCC tumors and the proliferation of HCC cells in vivo. Our findings suggest that AT2R overexpression regulates proliferation of hepatocellular carcinoma cells in vitro and in vivo, and the precise mechanisms of this phenomenon are yet to be fully determined.
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影响因子：
2.1
作者：
Horiuchi, M;Akishita, M;Dzau, VJ
通讯作者：
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影响因子：
4.7
作者：
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DOI：
10.1016/j.bbrc.2005.08.035
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影响因子：
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