Euphorbia Fischeriana Steud Inhibits Growth And Metastasis Of Melanoma Via Modulation Of PI3K/Akt Signaling Pathway

Purpose:To study relationship and mechanisms between the PI3K/Akt signaling pathway and inhibition effect of Euphorbia Fischeriana Steud on growth and metastasis of melanoma B16cells in vitro and in vivo.Methods:Malignat melanoma B16cells in this study were divided into vitro and vivo two parts. In vitro:The effects of Euphorbia Fischeriana Steud Extraction (LDE) on proliferation of B16cells were evaluated by MTT assays; Flow cytometry analysis (FCM) was used to detect the effect of LDE on cell cycle progression and the apoptosis ratios of B16cells; Assay of LDE on invasion ability of B16cells was measured by Transwell chamber method; Expression levels of PTEN and p-Akt in melanoma B16cells which were treated by LDE for24h were determined by Western blot technique; Detection of effect of LDE on expression of p-Akt, MMP-2and P70S6K1mRNA in melanoma B16cells was used Realtime-PCR technique. In vivo:The B16mouse transplanted tumor model and B16spontaneous motility melanoma metastatic model were established; C57BL/6mice were randomly divided into Control Group, Group LDE15.0g.kg-1, Group LDE20.0g.kg-1and CTX Group to detect the inhibition effect of LDE for growth of transplanted tumors and metastatic incidence on lung; The expression of PTEN and p-Akt of transplanted tumors were observed by immunohistochemical method.Results:(1) LDE at concentrations of0.8～2.0mg/ml inhibited the growth and the invasion of B16cells and induced apoptosis and G0/G1cell cycle arrest in both a time-and dose-dependent manner.(2) LDE could up-regulate PTEN and down-regulate p-Akt expression of B16cells, decrease the mRNA expression of p-Akt, MMP-2and P70S6K1, and eventually inhibits growth and metastasis of melanoma B16cells via modulation of PI3K/Akt signaling pathway.(3) LDE could significantly inhibit the growth of B16cells and the lung metastasis in vivo, up-regulate PTEN and down-regulate p-Akt expression of B16transplanted tumors which are related to the angiogenesis and metastasis of malignant B16melanoma.Conclusion:Euphorbia Fischeriana Steud could inhibit the growth and metastasis of B16cells in vitro and in vivo, probably via modulation of PI3K/Akt signaling pathway and up-regulating of PTEN while down-regulating of p-Akt expression, further study are warranted.