Gypenosides inhibits migration and invasion of human oral cancer SAS cells through the inhibition of matrix metalloproteinase-2-9 and urokinase-plasminogen by ERK1/2 and NF-kappa B signaling pathways
Gypenosides inhibits migration and invasion of human oral cancer SAS cells through the inhibition of matrix metalloproteinase-2-9 and urokinase-plasminogen by ERK1/2 and NF-kappa B signaling pathways
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DOI：
10.1177/0960327110372405
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发表时间：
2011-05-01
影响因子：
2.8
通讯作者：
Chung, Jing-Gung
中科院分区：
文献类型：
--
作者：
Lu, Kung-Wen;Chen, Jung-Chou;Chung, Jing-Gung
绞股蓝皂苷 (Gyp) 存在于绞股蓝中，几个世纪以来一直被中国人用作民间药物，并具有多种药理作用，包括抗增殖和抗癌作用。然而Gyp对预防口腔癌细胞侵袭和迁移的效果仍不理想。本研究的目的是探讨 Gyp 治疗对 SAS 人类口腔癌细胞迁移和侵袭的影响。 SAS细胞在90和180μg/mL Gyp存在下培养24和48小时。 Gyp 诱导细胞毒性作用，并以剂量和时间依赖性反应抑制 SAS 细胞迁移和侵袭。进行伤口愈合实验和博伊登室实验来研究Gyp抑制SAS细胞的迁移和侵袭。 Gyp 降低了多种蛋白质的丰度，包括核因子 kappa B (NF-kappa B)、环氧合酶-2 (COX-2)、细胞外信号调节激酶 1/2 (ERK1/2)、基质金属蛋白酶-9, -2 (MMP-9, -2)、七倍同源物 (SOS)、Ras、尿激酶型纤溶酶原激活剂 (uPA)、粘着斑激酶 (FAK)和 RAC-α 丝氨酸/苏氨酸蛋白激酶 (Akt)，以时间依赖性方式。此外，Gyp降低了SAS细胞中MMP-2、MMP-7、MMP-9的mRNA水平，但不影响FAK和Rho A mRNA水平。这些结果为Gyp作为有效抗转移剂的作用提供了证据，它可以显着抑制口腔癌细胞的转移和侵袭能力。 NF-κ B 和 MMP-2、-7 和 -9 信号传导的抑制可能是 Gyp 抑制癌细胞侵袭和迁移的机制之一。
Gypenosides (Gyp), found in Gynostemma pentaphyllum Makino, has been used as a folk medicine in the Chinese population for centuries and is known to have diverse pharmacologic effects, including anti-proliferative and anti-cancer actions. However, the effects of Gyp on prevention from invasion and migration of oral cancer cells are still unsatisfactory. The purpose of this study was to investigate effects of Gyp treatment on migration and invasion of SAS human oral cancer cells. SAS cells were cultured in the presence of 90 and 180 mu g/mL Gyp for 24 and 48 hours. Gyp induced cytotoxic effects and inhibited SAS cells migration and invasion in dose-and time-dependent response. Wound-healing assay and boyden chamber assay were carried out to investigate Gyp-inhibited migration and invasion of SAS cells. Gyp decreased the abundance of several proteins, including nuclear factor-kappa B (NF-kappa B), cyclooxygenase-2 (COX-2), extracellular signal-regulated kinase 1/2 (ERK1/2), matrix metalloproteinase-9, -2 (MMP-9, -2), sevenless homolog (SOS), Ras, urokinase-type plasminogen activator (uPA), focal adhesion kinase (FAK) and RAC-alpha serine/threonine-protein kinase (Akt), in a time-dependent manner. In addition, Gyp decreased mRNA levels of MMP-2, MMP-7, MMP-9 but did not affect FAK and Rho A mRNA levels in SAS cells. These results provide evidences for the role of Gyp as a potent anti-metastatic agent, which can markedly inhibit the metastatic and invasive capacity of oral cancer cells. The inhibition of NF-kappa B and MMP-2, -7 and -9 signaling may be one of the mechanisms that is present in Gyp-inhibited cancer cell invasion and migration.