蛇葡萄素体内外对小鼠B16黑色素瘤侵袭和转移的抑制作用

Effects of Ampelopsin on Invasion and Metastasis of B16 Mouse Melanoma in vivo and in vitro

目的 :研究蛇葡萄素对B16小鼠黑色素瘤体内外抗侵袭和转移的作用。方法 :B16细胞由尾静脉注入C5 7BL/ 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 18d ,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 3d ,用具有聚碳酸酯和重建基底膜 (Matrigel)的Tran swell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 :剂量为 15 0 ,2 0 0 ,2 5 0mg·kg-1的蛇葡萄素可抑制小鼠肺转移瘤灶形成 ,与溶剂对照组比 ,抑制率分别为 30 .97% ,4 0 .5 8% ,6 1.16 % (P <0 .0 5 )。经 2 0 ,4 0 ,80 μmol·L-1各浓度蛇葡萄素处理后 ,对B16细胞侵袭人工基底膜的抑制率分别为 36 .0 6 % ,5 9.5 8% ,79.0 9% (P <0 .0 1) ;对细胞的趋化运动抑制率分别为 5 1.5 9% ,5 6 .5 1% ,6 6 .75 % (P <0 .0 1) ;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。

Objective: To investigate the effects of ampelopsin on B16 melanoma's invasion and metastasis in vivo and in vitro. Method: B16 mouse melanoma cells were injected into C57BL/6 mouse via tail lateral vein, which subsequently colonized into the animal lungs to form an experimental pulmonary metastasis of tumor cell. The ampelopsin was administered at 3 dosages by intraperitoneal injection daily for 18 days from the day before the cells injection. The B16 mouse melanoma cells were exposed to ampelopsin for 3 days. The effects of ampelopsin on invasion, migration and adhesion of B16 melanoma cells were evaluated with Transwell chambers or attachment with polycarbonate filters and reconstituted basement membrane (Matrigel). Result: The number of metastases in the animals that were given ampelopsin 150, 200, and 250 mg·kg -1 ·d -1 was significantly reduced as compared to the vehicle 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 was decreased significantly( P <0.01), and the inhibition rates were 36.06%,59.58%, and 79.09% at 20 μmol·L -1 , 40 μmol·L -1 and 80 μmol·L -1 concentration, respectively. Ampelopsin could also inhibit B16 cells migration through PVPF in the Transwell chambers, and the inhibition rates were 51.59%, 56.51%, and 66.75% at 20 μmol·L -1 , 40 μmol·L -1 and 80 μmol·L -1 , respectively ( P <0.01). The ability of adhesion of the B16 cells by ampelopsin treated cells on fibronectin, laminin, or Matrigel was decreased significantly. Conclusion: Ampelopsin has anti-invasive and anti-metastatic effects on B16 melanoma.