Shinkai K, Akedo H, Mukai M, Imamura F, Isoai A, Kobayashi M, Kitagawa I
Department of Tumor Biochemistry, The Center for Adult Diseases Osaka, Japan.
Jpn J Cancer Res. 1996 Apr;87(4):357-62. doi: 10.1111/j.1349-7006.1996.tb00230.x.
The effect of plant glycosides on tumor cell invasion was examined. Among the glycosides tested, ginsenoside Rg3 was found to be a potent inhibitor of invasion by rat ascites hepatoma cells (MM1), B16FE7 melanoma cells, human small cell lung carcinoma (OC10), and human pancreatic adenocarcinoma (PSN-1) cells, when examined in a cell monolayer invasion model. Structurally analogous ginsenosides, Rb2, 20(R)-ginsenoside Rg2 and 20(S)-ginsenoside Rg3 (a stereoisomer of Rg3), showed little inhibitory activity. Neither Rh1, Rh2, 20(R)-ginsenosides Rh1, Rb1, Rc nor Re had any effect. The effective ginsenoside, Rg3, tended to inhibit experimental pulmonary metastasis by highly metastatic mouse melanoma B16FE7 cells as well. Taking account of our previous finding that 1-oleoyl-lysophosphatidic add (LPA) induced invasion by MM1 cells in the monolayer invasion model, the effect of Rg3 on molecular events associated with the invasion induced by LPA was analyzed in order to understand the mechanism of the inhibition. Rg3, which suppressed the invasion induced by LPA, dose-dependently inhibited the LPA-triggered rise of intracellular Ca2+. Protein tyrosine phosphorylation triggered by LPA was not inhibited by Rg3.
研究了植物糖苷对肿瘤细胞侵袭的影响。在测试的糖苷中,当在细胞单层侵袭模型中检测时,发现人参皂苷Rg3是大鼠腹水肝癌细胞(MM1)、B16FE7黑色素瘤细胞、人小细胞肺癌(OC10)和人胰腺腺癌(PSN-1)细胞侵袭的有效抑制剂。结构类似的人参皂苷Rb2、20(R)-人参皂苷Rg2和20(S)-人参皂苷Rg3(Rg3的立体异构体)显示出几乎没有抑制活性。Rh1、Rh2、20(R)-人参皂苷Rh1、Rb1、Rc和Re均无任何作用。有效的人参皂苷Rg3也倾向于抑制高转移性小鼠黑色素瘤B16FE7细胞的实验性肺转移。考虑到我们之前的发现,即1-油酰-溶血磷脂酸(LPA)在单层侵袭模型中诱导MM1细胞侵袭,分析了Rg3对与LPA诱导的侵袭相关的分子事件的影响,以了解抑制机制。抑制LPA诱导侵袭的Rg3剂量依赖性地抑制LPA触发的细胞内Ca2+升高。Rg3不抑制LPA触发的蛋白质酪氨酸磷酸化。