The A3 adenosine receptor agonist CF102 induces apoptosis of hepatocellular carcinoma via de-regulation of the Wnt and NF-κB signal transduction pathways
The A3 adenosine receptor agonist CF102 induces apoptosis of hepatocellular carcinoma via de-regulation of the Wnt and NF-κB signal transduction pathways
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DOI：
10.3892/ijo_00000008
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发表时间：
2008-08-01
影响因子：
5.2
通讯作者：
Fishman, P.
中科院分区：
文献类型：
--
作者：
Bar-Yehuda, S.;Stemmer, S. M.;Fishman, P.
A（3）腺苷受体（A（3）AR）在肿瘤中高度表达，并被建议作为癌症治疗的靶点。在这项研究中，我们发现A（3）AR在肿瘤组织和来自HCC患者的外周血单个核细胞（PBMC）中高度表达，以及来自HCC荷瘤大鼠。该受体的高表达水平与NF-κ B的过表达直接相关，NF-κ B是A（3）AR的转录因子。CF 102是一种合成的A3 AR高选择性激动剂，通过NF-κ B和Wnt信号转导通路的失调，诱导N1 S1 HCC肿瘤大鼠肿瘤生长的显著剂量反应抑制，导致肿瘤细胞凋亡。综上所述，A（3）AR在HCC患者和荷瘤大鼠的肿瘤和PBMC中高度表达。CF 102诱导细胞凋亡和抑制肿瘤生长。这些数据表明A（3）AR是治疗HCC的一种新的靶向疗法。
The A(3) adenosine receptor (A(3)AR) is highly expressed in tumors and was suggested as a target for cancer treatment. In this study, we show that A(3)AR is highly expressed in tumor tissues and in peripheral blood mononuclear cells (PBMCs) derived from patients with HCC, as well as from HCC tumor-bearing rats. The high expression level of the receptor was directly correlated to overexpression of NF-kappa B, known as a transcription factor of A(3)AR. CF102, a synthetic highly selective agonist to A3AR induced a marked dose response inhibition of tumor growth in N1S1 HCC tumor rats, via de-regulation of the NF-kappa B and the Wnt signal transduction pathways, resulting in apoptosis of tumor cells. Taken together, A(3)AR is highly expressed in tumors and PBMCs of HCC patients and tumor-bearing rats. CF102 induced apoptosis and tumor growth inhibition. These data suggest A(3)AR as a novel targeted therapy to treat HCC.