Saikosaponin-d suppresses the expression of cyclooxygenase-2 through the phospho-signal transducer and activator of transcription 3/hypoxia-inducible factor-1α pathway in hepatocellular carcinoma cells
Saikosaponin-d suppresses the expression of cyclooxygenase-2 through the phospho-signal transducer and activator of transcription 3/hypoxia-inducible factor-1α pathway in hepatocellular carcinoma cells
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DOI：
10.3892/mmr.2014.2574
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发表时间：
2014-11-01
影响因子：
3.4
通讯作者：
Wang, Zhilun
中科院分区：
文献类型：
--
作者：
He, Shuixiang;Lu, Guifang;Wang, Zhilun
肝细胞癌（HCC）是最常见的恶性肿瘤之一，占全球所有类型人类癌症的6%，特别是在亚洲。美国的发病率和死亡率也迅速上升。柴胡皂苷d（Saikosaponin-d，SSD）是从伞形科柴胡属植物中提取的一种皂苷衍生物，具有抗炎、抗肝炎、免疫调节等独特的生物活性。我们的前期研究表明，SSD通过下调环氧合酶（考克斯）-2的表达和减少前列腺素E2的产生，抑制肝癌SMMC-7721细胞的增殖，诱导其凋亡。然而，SSD如何控制考克斯-2表达的具体机制仍有待阐明。本研究证实低氧诱导因子-1 α（HIF-1 alpha）参与了肝癌细胞在低氧条件下考克斯-2的表达，而信号转导和转录激活因子3（STAT 3）的激活是HIF-1 α表达所必需的。SSD处理抑制STAT 3活化[STAT 3的磷酸化（p-STAT 3）]，降低HIF-1 α的蛋白水平并降低考克斯-2的表达。这些结果表明SSD可以靶向HCC细胞。通过p-STAT 3/HIF-1 α途径抑制考克斯-2的表达。
Hepatocellular carcinoma (HCC) is one of the most common malignancies and accounts for similar to 6% of all types of human cancer worldwide, particularly in Asia. The incidence and mortality rates in the USA have also rapidly increased. Saikosaponin-d (SSD), a saponin derivative extracted from several species of Bupleurum (Umbelliferae), possesses unique biological activities, including anti-inflammatory, antihepatitic and immunomodulatory effects. Our previous studies have demonstrated that SSD inhibits the proliferation and induces the apoptosis of HCC SMMC-7721 cells by downregulating the expressiOn of cyclooxygenase (COX)-2 and decreasing the production of prostaglandin E2. However, the specific mechanism underlying how SSD controls the expression of COX-2 remains to be elucidated. In the present study, it was demonstrated that hypoxia inducible factor-1 alpha (HIF-1 alpha) was responsible for the expression of COX-2 under hypoxic conditions in HCC cells, and the activation of signal transducer and activator of transcription 3 (STAT3) was required for the expression of HIF-1 alpha. SSD treatment inhibited STAT3 activation [phosphorylation of STAT3 (p-STAT3)], reduced the protein level of HIF-1 alpha and decreased the expression of COX-2. These results suggested that SSD may target HCC cells. by suppressing the expression of COX-2 through the p-STAT3/HIF-1 alpha pathway.