The in vitro antitumor activity of Siegesbeckia glabrescens against ovarian cancer through suppression of receptor tyrosine kinase expression and the signaling pathways
The in vitro antitumor activity of Siegesbeckia glabrescens against ovarian cancer through suppression of receptor tyrosine kinase expression and the signaling pathways
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DOI：
10.3892/or.2013.2468
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发表时间：
2013-07-01
期刊：
影响因子：
4.2
通讯作者：
Seo, Dong-Wan
中科院分区：
文献类型：
--
作者：
Cho, Young-Rak;Choi, Shin Wook;Seo, Dong-Wan
光肩星天麻是菊科植物，被用作治疗过敏、炎症、急性肝炎和高血压等多种疾病的传统药物。本研究的主要目的是确定SG的乙醇提取物是否具有抗卵巢癌的活性，并确定参与调控细胞生长和进展的分子机制和靶点。我们证明SG处理抑制了SKOV-3人卵巢癌细胞的增殖、黏附、迁移和侵袭。SG对SKOV-3细胞的抗增殖作用伴随着细胞周期蛋白E表达的降低和细胞周期蛋白依赖性激酶抑制因子p27(KIPL)的表达增强，从而抑制pRb的磷酸化。我们还发现，这些抗肿瘤活性是通过抑制依赖于FAK、ERK、Akt和p70(S6K)的信号通路以及下调受体酪氨酸激酶如EGFR、VEGFR-2和FGFR-1以及细胞黏附分子N-钙粘素来实现的。综上所述，我们的研究结果建议进一步开发和评估SG治疗卵巢癌。
Siegesbeckia glabrescens (SG) Makino (Compositae) has been used as a traditional medicine for the treatment of a variety of diseases such as allergy, inflammation, acute hepatitis and hypertension. The primary aim of this study was to determine whether the ethanol extract of SG has antitumor activity against ovarian cancer and to identify molecular mechanisms and targets involved in the regulation of cell growth and progression. We demonstrate that SG treatment inhibits proliferation, adhesion, migration and invasion of SKOV-3 human ovarian cancer cells. The anti-proliferative effect of SG on SKOV-3 cells is accompanied by reduced expression of cyclin E and enhanced expression of the cyclin-dependent kinase inhibitor p27(Kipl), leading to inhibition of pRb phosphorylation. We also show that these antitumor activities are found to be mediated through suppression of FAK, ERK, Akt and p70(S6K)-dependent signaling pathways and downregulation of receptor tyrosine kinases such as EGFR, VEGFR-2 and FGFR-1 as well as the cell adhesion molecule N-cadherin. Taken together, our findings suggest further development and evaluation of SG for the treatment of ovarian cancer.