蛇葡萄素抗黑色素瘤侵袭和转移的作用

Anti-invasive and Anti-metastatic Effect of Ampelopsin on Melanoma

背景与目的:我们先前的研究发现蛇葡萄素在体外对几种人肿瘤细胞以及在体内对小鼠移植性B16黑色素瘤具有抑制作用。为了进一步研究其抑制肿瘤转移的作用,我们研究了蛇葡萄素在体内外抗B16小鼠黑色素瘤侵袭和转移的作用。方法:B16细胞由尾静脉注入C57BL/6小鼠体内,建立实验性肺转移模型,蛇葡萄素以3个剂量从接种瘤细胞前一天腹腔给药,连续18天,于停药后第2天观察肺转移瘤灶数。B16细胞经蛇葡萄素处理3天,用具有聚碳酸酯和重建基底膜(基质胶Matrigel)的Transwell小室侵袭模型,研究药物处理后细胞侵袭、趋化运动、粘附能力的改变。结果:150、200、250mg/kg的蛇葡萄素可抑制小鼠肺转移瘤灶形成,与对照组比,抑制率分别为30.97%、40.58%、61.16%(P<0.05)。经20、40、80μmol/L蛇葡萄素处理后,对B16细胞侵袭人工基底膜的抑制率分别为36.06%、59.58%和79.09%(P<0.01);对细胞的趋化运动抑制率分别为51.59%、56.51%和66.75%(P<0.01);显著降低B16细胞与基质成分层粘连蛋白、纤维粘连蛋白及Matrigel的粘附作用。结论:蛇葡萄素具有抑制黑色素瘤的侵袭和转移的作用。

BACKGROUND ＆OBJECTIVE: The authors had firstly reported that ampelopsin possess anticancer effects on several human cancer cell lines in vitro and on transplant mouse B16 melanoma in vivo. In order to further explore its antitumor effect, the authors designed this study to investigate the effect of ampelopsin on invasion and metastasis of B16 melanoma in vivo and in vitro. METHODS: B16 cells were injected into C57BL/6 mouse via tail lateral vein, and subsequently formed an experimental pulmonary metastasis. Ampelopsin was administered at 3 dosages by intraperitoneal injection daily for 18 days from the day before cell injection. The B16 mouse melanoma cells were treated with ampelopsin for 3 days. The effect of ampelopsin on invasion, migration，and adhesion of B16 melanoma cells were evaluated using Transwell chambers attached with polycarbonate filters and reconstituted basement membrane (Matrigel). RESULTS:The number of metastases in the mice that were given ampelopsin at the dosages of 150, 200, and 250 mg/kg significantly reduced as compared to the control (P< 0 05),and the inhibition rates were 30 97％,40 58％,and 61 16％,respectively. The ability of the ampelopsin treated B16 cells to invade the reconstituted basement membrane decreased significantly (P< 0 01), and the inhibition rates were 36 06％，59 58％, and 79 09％〓for ampelopsin at 20, 40, and 80 μmol/L,respectively.Ampelopsin can also inhibit B16 cells migration,and the inhibition rates were 51 59％,56 51％,and 66 75％〓for ampelopsin at 20,40,and 80 μmol/L,respectively(P< 0 01).The ability of adhesion of the B16 cells with fibronectin,laminin,or Matrigel decreased significantly. CONCLUSION: Ampelopsin has anti invasive and anti metastatic effects on B16 melanoma.