The inhibitor of Ca2+-dependent K+ channels TRAM-34 blocks growth of hepatocellular carcinoma cells via downregulation of estrogen receptor alpha mRNA and nuclear factor-kappaB
The inhibitor of Ca2+-dependent K+ channels TRAM-34 blocks growth of hepatocellular carcinoma cells via downregulation of estrogen receptor alpha mRNA and nuclear factor-kappaB
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DOI：
10.1007/s10637-012-9879-6
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发表时间：
2013-04-01
影响因子：
3.4
通讯作者：
Somasundaram, Rajan
中科院分区：
文献类型：
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作者：
Freise, Christian;Ruehl, Martin;Somasundaram, Rajan
肝细胞癌（HCC）是最常见的肝脏恶性肿瘤，仍然需要新的治疗方案。由于离子通道抑制剂TRAM-34（1-[（2-氯苯基）二苯基甲基]- 1h -吡唑）可以阻断多种癌细胞的生长，我们研究了TRAM-34在人HCC细胞系中的抗肿瘤作用。我们发现TRAM-34在不诱导细胞凋亡的情况下降低了HCC细胞的增殖。这是由于雌激素受体α (ESR1)的mRNA表达减少和NF-kappaB的激活减少，这两者都与HCC的发展有关。因此，TRAM-34可能是治疗HCC的一个新的治疗靶点。
Hepatocellular carcinoma (HCC) is the most common liver malignancy still demanding for novel therapeutic options. Since the ion channel inhibitor TRAM-34 (1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole) was shown to block growth in various cancer cells, we investigated anti-tumor effects of TRAM-34 in human HCC cell lines. We found that TRAM-34 reduced HCC cell proliferation without induction of apoptosis. This was due to a decreased mRNA expression of estrogen receptor alpha (ESR1) and a reduced activation of NF-kappaB, which both are implicated in the development of HCC. Therefore, TRAM-34 might represent a novel therapeutic target for the treatment of HCC.