摘要
为了获得具有显著抑瘤活性的水溶性海参皂苷样品,利用大孔树脂柱、硅胶柱和葡聚糖凝胶柱对水溶性海参皂苷进行了分离纯化,并对其体内外抑瘤活性和诱导肿瘤细胞凋亡进行了检测。研究结果显示,大孔树脂柱的70%乙醇洗脱组分以及硅胶柱色谱的部分纯化组分(pSC-2和pSC-3)对HeLa细胞、A-549肺癌细胞、SGC-7901胃癌细胞和Bel-7402肝癌细胞均具有显著的抑瘤活性;经过葡聚糖凝胶柱色谱,获得了纯度均在99.6%以上、具有三萜类皂苷性质的SC-2和SC-3纯化样品,发现SC-2纯化样品不仅能浓度和时间依赖性地抑制HeLa细胞的体外增殖,还能剂量依赖性地抑制S180实体瘤的体内生长,提高荷瘤小鼠的胸腺指数和脾指数。细胞凋亡检测结果显示,SC-2纯化样品可剂量依赖性地诱导HeLa细胞凋亡,SC-2纯化样品(10和50mg.L-1)处理12h的HeLa细胞均出现了DNA片段化。可见,水溶性海参皂苷SC-2纯化样品具有显著的抑瘤活性,其机制可能是通过诱导肿瘤细胞发生凋亡来实现的。
To obtain water-soluble holothurian glycosides with high tumor suppressing activities from Apostichopus japonicus, macroporous resin, silica gel and gel-filtration column chromatograghy were used to purify the water-soluble holothurian glycosides, and their tumor suppressing activity and inducing apoptosis of tumor cells were examined in this study. The 70% ethanol fraction of macroporous resin column, the pSC-2 and pSC-3 fractions from silica gel column showed very strong tumor suppressing activity towards HeLa cells, A-549 lung cancer ceils, SGC-7901 stomach cancer cells and Bel-7402 liver cancer ceils. SC-2 and SC-3 fraction purified from Sephadex LH-20 gel-filtration column chromatography, with a purity above 99.6%, all had the properties of triterpenoid glycosides. Purified SC-2 fraction had remarkable tumor suppressing activity on HeLa cells in a doseand time-dependent manner, and had prominent tumor suppressing activity to mouse S180 solid tumors in a dose-dependent manner. Besides, the SC-2 fraction also had remarkable ability in elevating mouse thymus index and spleen index. The purified SC-2 fraction could induce apoptosis of HeLa cells in a dose-dependent manner, and DNA fragmentation of HeLa cells occurred after treated 12 h with 10 mg·L^-1 and 50 mg·L^-1 of SC-2 fractions. From the results, it can be concluded that the purified SC-2 fraction of water-soluble holothurian glycosides has extremely strong tumor suppressing activity, and the suppression is realized by inducing tumor cells to undergo apoptosis. This study lays solid foundation for development of highly effective new natural anticancer agents fromsea cucumbers.
出处
《药学学报》
CAS
CSCD
北大核心
2009年第1期25-31,共7页
Acta Pharmaceutica Sinica
基金
山东省优秀中青年科学家科研奖励基金资助项目(03BS110)
关键词
水溶性海参皂苷
抑瘤活性
细胞凋亡
大孔树脂柱
硅胶柱
凝胶柱色谱
water-soluble holothurian glycoside
tumor suppressing activity
apoptosis
macroporous resincolumn
silica gel column
gel-filtration colunm chromatography
