Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, PR China.
Phytomedicine. 2012 Feb 15;19(3-4):355-63. doi: 10.1016/j.phymed.2011.09.070. Epub 2011 Oct 5.
Oxidative stress plays an important role in tumorigenesis and metastasis. Salidroside, a phenylpropanoid glycoside isolated from Rhodiola rosea L., shows potent antioxidant property. Here we investigated the inhibitory effects of salidroside on tumor metastasis in human fibrosarcoma HT1080 cells in vitro. The results indicated that salidroside significantly reduced wound closure areas of HT1080 cells, inhibited HT1080 cells invasion into Matrigel-coated membranes, suppressed matrix metalloproteinases (MMP-2 and MMP-9) activity, and increased tissue inhibitor of metalloproteinase-2 (TIMP-2) expression in a dose-dependent manner in HT1080 cells. Salidroside treatment upregulated the E-cadherin expression, while downregulated the expression of β1-integrin. As an antioxidant, salidroside inhibited the intracellular reactive oxygen species (ROS) formation in a dose-dependent manner. The results also showed that salidroside could inhibit the activation of protein kinase C (PKC) and the phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) in a dose-dependent manner. In conclusion, these results suggest that salidroside inhibits tumor cells metastasis, which may due to its interfere in the intracellular excess ROS thereby down-regulated the ROS-PKC-ERK1/2 signaling pathway.
氧化应激在肿瘤发生和转移中起着重要作用。红景天苷是从红景天中分离得到的苯丙素糖苷,具有很强的抗氧化活性。本研究探讨了红景天苷对体外人纤维肉瘤 HT1080 细胞转移的抑制作用。结果表明,红景天苷能显著减少 HT1080 细胞的划痕愈合面积,抑制 HT1080 细胞侵袭 Matrigel 包被膜,抑制基质金属蛋白酶(MMP-2 和 MMP-9)活性,并呈剂量依赖性增加 HT1080 细胞中组织金属蛋白酶抑制剂-2(TIMP-2)的表达。红景天苷处理上调 E-钙黏蛋白的表达,同时下调β1-整合素的表达。作为一种抗氧化剂,红景天苷能剂量依赖性地抑制细胞内活性氧(ROS)的形成。结果还表明,红景天苷能剂量依赖性地抑制蛋白激酶 C(PKC)的激活和细胞外信号调节激酶 1 和 2(ERK1/2)的磷酸化。综上所述,这些结果表明红景天苷抑制肿瘤细胞转移,这可能是由于其干扰细胞内过量的 ROS,从而下调 ROS-PKC-ERK1/2 信号通路。