白术内酯Ⅰ体内外的抗黑色素瘤研究

Study on inhibiting effects of atractylenolide I against melanoma in vitro and in vivo

目的:探讨白术内酯I对人黑色素瘤细胞A875的作用、对肿瘤血管生成的作用和对小鼠黑色素瘤荷瘤小鼠肿瘤生长的抑制作用及其机制。方法:MTT法检测白术内酯I对A875细胞增殖的影响,流式细胞仪检测白术内酯I对A875细胞周期及其凋亡的影响;白术内酯I对体外血管内皮细胞成管的影响;白术内酯I对荷瘤小鼠肿瘤生长及小鼠体质量的影响。结果:白术内酯I抑制黑色素瘤细胞A875细胞增殖;作用48 h后,细胞周期中G2/M期和S期细胞比例显著提高,G0/G1期细胞比例减少;细胞凋亡比例显著增加;白术内酯I显著抑制内皮细胞成管;白术内酯I显著抑制荷瘤小鼠肿瘤的生长,而对小鼠体质量无影响。结论:白术内酯I抑制黑色素瘤细胞A875增殖,诱导细胞凋亡,发生细胞周期阻滞;并且能够抑制荷瘤小鼠肿瘤生长,不影响荷瘤小鼠的体质量。

OBJECTIVE To investigate the inhibiting effects of atractylenolide I against proliferation of human melanoma cell line A875, tumor angiogenesis and growth of primary melanoma in mice. METHODS Inhibition activity of atractylenolide I a- gainst cell line A875 was estimated by MTT assay. Flow cytometry was used to analyze the effects of atractylenolide I on cell cycle distribution and cell apoptosis, endothelial angiogenesis, and growth of tumor and body mass of tumor bearing mice. RE- SULTS Atractylenolide I could inhibit proliferation of A875. When treated with atractylenolide I for 48 h, cells at early stage of apoptosis showed morphologic changes, apoptotic cells increased, ceils at G0/1 phase decreased and those at G2/M and S phase increased. Atractylenolide I could inhibit tumor angiogenesis. In vivo, tumor size of primary melanoma in mice intraper itoneally treated with atractylenolide I was significantly smaller than that of the control. CONCLUSION Atractylenolide I can inhibit proliferation of A875, which may relate to induction of cell apoptosis and inhibition of cell cycle progress. Atractylenol- ide I can also inhibit melanoma growth.