Kim Mi Suk, Park Myung Jin, Kim So Jeong, Lee Chang Hun, Yoo Heon, Shin Sang Hoon, Song Eun Sook, Lee Seung Hoon
Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Korea.
Int J Oncol. 2005 Sep;27(3):839-46.
Emodin, an inhibitor of protein tyrosine kinase, possesses antiviral, immunosuppressive, anti-inflammatory and anticancer effects. In the present study, we investigated the effect of emodin on the hyaluronic acid (HA)-induced invasion of human glioma cells. Emodin significantly inhibited the HA-induced invasion through a Matrigel coated chamber, secretion of matrix metalloproteinase (MMP)-2, and HA-induced secretion of MMP-9 in glioma cells. To investigate the possible mechanisms involved in these events, we performed Western blot analysis using phospho-specific antibodies, and found that emodin inhibited phosphorylation of focal adhesion kinase (FAK), extracellular regulated protein kinase (ERK) 1/2 and Akt/PKB; emodin also suppressed the transcriptional activity of two transcription factors, activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB), in glioma cells. In addition, oral administration of emodin suppressed in vivo MMP secretion by glioma tumors in nude mice. Taken together, our results indicate that emodin can effectively inhibit HA-induced MMP secretion and invasion of glioma through inhibition of FAK, ERK1/2 and Akt/PKB activation and partial inhibition of AP-1 and NF-kappaB transcriptional activities. Consequently, these results provide important insights into emodin as an anti-invasive agent for the therapy of human glioma.
大黄素是一种蛋白酪氨酸激酶抑制剂，具有抗病毒、免疫抑制、抗炎和抗癌作用。在本研究中，我们研究了大黄素对透明质酸（HA）诱导的人胶质瘤细胞侵袭的影响。大黄素显著抑制了HA诱导的通过基质胶包被小室的侵袭、基质金属蛋白酶（MMP）-2的分泌以及HA诱导的胶质瘤细胞中MMP-9的分泌。为了研究这些事件中可能涉及的机制，我们使用磷酸化特异性抗体进行了蛋白质印迹分析，发现大黄素抑制了粘着斑激酶（FAK）、细胞外调节蛋白激酶（ERK）1/2和Akt/PKB的磷酸化；大黄素还抑制了胶质瘤细胞中两种转录因子激活蛋白-1（AP-1）和核因子-κB（NF-κB）的转录活性。此外，口服大黄素可抑制裸鼠体内胶质瘤肿瘤的MMP分泌。综上所述，我们的结果表明，大黄素可通过抑制FAK、ERK1/2和Akt/PKB的激活以及部分抑制AP-1和NF-κB的转录活性，有效抑制HA诱导的MMP分泌和胶质瘤侵袭。因此，这些结果为大黄素作为治疗人类胶质瘤的抗侵袭药物提供了重要的见解。
