Xanthohumol inhibits STAT3 activation pathway leading to growth suppression and apoptosis induction in human cholangiocarcinoma cells
Xanthohumol inhibits STAT3 activation pathway leading to growth suppression and apoptosis induction in human cholangiocarcinoma cells
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DOI：
10.3892/or.2016.4584
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发表时间：
2016-04-01
期刊：
影响因子：
4.2
通讯作者：
Loilome, Watcharin
中科院分区：
文献类型：
--
作者：
Dokduang, Hasaya;Yongvanit, Puangrat;Loilome, Watcharin
STAT 3在与肝吸虫（Opisthorchis viverrini; Ov）相关的胆管癌（CCA）的发展中起重要作用。黄腐酚（XN）是一种从啤酒花中提取的异戊烯化类黄酮，具有已知的抗癌活性，可能靶向STAT 3。本研究确定XN对STAT 3的影响，以及确定其对CCA的有用性。20 μ M和50 μ M的XN抑制CCA细胞增殖，而20 μ M部分抑制IL-6诱导的STAT 3活化。在50 μ M时，抑制完全。STAT 3活性在20和50 μ M的减少与CCA细胞生长和凋亡的显着减少。我们还发现，与对照组相比，接种CCA的裸鼠口服50 μ M XN饮用水导致肿瘤生长减少。此外，癌细胞凋亡增加，但没有可见的毒性。目前的研究表明，XN可以抑制STAT 3激活在体内和体外由于抑制Akt-NF κ B信号通路。XN可能是一种治疗CCA的药物。
STAT3 plays a significant role in the development of cholangiocarcinoma (CCA) associated with the liver fluke (Opisthorchis viverrini; Ov). Xanthohumol (XN), a prenylated flavonoid extracted from hops, has known anticancer activity and could potentially target STAT3. The present study determined the effect of XN on STAT3, as well as ascertained its usefulness against CCA. The CCA cell proliferation at 20 mu M and 50 mu M of XN was shown to inhibited, while 20 mu M partially inhibited IL-6-induced STAT3 activation. At 50 mu M, the inhibition was complete. The reduction in STAT3 activity at 20 and 50 mu M was associated with a significant reduction of CCA cell growth and apoptosis. We also found that the administration of 50 mu M XN orally in drinking water to nude mice inoculated with CCA led to a reduction in tumor growth in comparison with controls. In addition, apoptosis of cancer cells increased although there was no visible toxicity. The present study shows that XN can inhibit STAT3 activation both in vivo and in vitro due to suppression of the Akt-NF kappa B signaling pathway. XN should be considered as a possible therapeutic agent against CCA.