天然二萜类衍生物DS2抑制胃癌细胞增殖及迁移
朱英丽;王爱凤;范霞霞;赵宁民;马永成
【期刊名称】《中华肿瘤杂志》 【年(卷),期】2018(040)007
【摘要】目的 探讨合成的对映-贝壳杉烷型二萜类衍生物DS2抗胃癌细胞增殖及迁移的作用及其可能机制.方法 采用四甲基偶氮唑蓝法、平板克隆实验和流式细胞术检测DS2对胃癌细胞增殖的影响,采用划痕实验和 Transwell 实验检测 DS2 对胃癌细胞 MGC-803 迁移的抑制作用,采用Western blot检测 DS2 对细胞迁移相关蛋白表达的影响.结果 DS2 可抑制胃癌细胞增殖. 6.25 μmol/L DS2作用MGC-803、SGC-7901 和 HGC-27 胃癌细胞24 h 后,细胞的生存率分别为( 53.87 ± 3.05)%、(55.91±6.97)% 和(32.41±2.64)%;DS2对胃癌细胞的抑制活性呈剂量依赖性,而对正常胃黏膜细胞GES-1影响不大,其生存率为(83.47±1.77)%. DS2可将胃癌细胞 MGC-803周期阻滞在G2/M期,同时诱导其凋亡,DS2以阻滞细胞周期和诱导凋亡的方式抑制胃癌细胞的生长增殖. DS2对MGC-803细胞的单克隆形成及迁移能力均有明显的抑制作用,并呈现剂量依赖性;DS2作用于MGC-803后可上调E-cadherin的表达,下调β-catenin和N-cadherin蛋白的表达.结论 新化合物DS2具有强烈的抗胃癌活性,为设计合成更多、更有效的二萜类抗肿瘤衍生物奠定基础.%Objective To investigate the effects and the underlying mechanism of DS2, a newly synthetic analog of natural ent-kaurane diterpenoid, on the proliferation and migration capabilities of human gastric cancer cells. Methods MTT assay, colony formation assay and flow cytometry were used to measure the
effects of DS2 on growth, apoptosis and cell cycle of several human gastric cancer cell lines.The function of DS2 in the migration was further detected by wound healing and transwell assays. The expression of migration related proteins were determined by western blot. Results DS2 inhibited the growth of MGC-803, SGC-7901 and HGC-27 cells in a dose dependent manner. After treatment of DS2 at a concentration of 6.25 μmol/L for 24 h, the survival rates of MGC-803, SGC-7901 and HGC-27 cells were 53.87±3.05%, 55.91± 6.97% and 32.41±2.64%, respectively. However, for the normal gastric epithelial cell GES-1, no obvious growth inhibition was observed. In addition, DS2 caused significant G2/M arrest and induced apoptosis in MGC-803 cells. Furthermore, compared with the negative control, the colony formation, wound healing rate as well as the number of migrating cells of MGC-803 were significantly decreased in a dose dependent manner after DS2 treatment. DS2 induced the expression of E-cadherin, whereas β-catenin and N-cadherin levels were downregulated in MGC-803. Conclusion The new compound DS2 has a strong anti-cancer activity, and this study will help us to design and synthesize better diterpenoids derivatives. 【总页数】6页(493-498)
【关键词】胃肿瘤;天然对映-贝壳杉烷型二萜类化合物;衍生物;增殖;迁移 【作者】朱英丽;王爱凤;范霞霞;赵宁民;马永成
【作者单位】450003 郑州大学人民医院药学部临床药理室;451464 郑州,阜外
华中心血管病医院药学部;450003 郑州大学人民医院药学部临床药理室;450003 郑州大学人民医院药学部临床药理室;451464 郑州,阜外华中心血管病医院药学部 【正文语种】中文 【中图分类】 【文献来源】
https://www.zhangqiaokeyan.com/academic-journal-cn_chinese-journal-oncology_thesis/0201236712940.html 【相关文献】
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天然二萜类衍生物DS2抑制胃癌细胞增殖及迁移
