小檗碱及其亲脂性衍生物抑制恶性胶质瘤C6细胞的增殖及迁移与侵袭  

Berberine and Its Lipophilic Derivatives Inhibit Proliferation, Migration and Invasion of Malignant Glioma C6 Cells

作　　者：付胜楠[1] 张国光[1] 庹珏[1] 杨小晓[2] 朱文博[2] 颜光美[2] 胡海燕[1] 

机构地区：[1]中山大学药学院∥药物制剂工程研究开发中心,广东广州510006 [2]中山大学中山医学院药理教研室,广东广州510081

出　　处：《中山大学学报（医学科学版）》2013年第4期531-536,F0002,共7页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：广东省自然科学基金(S2012010009237)

摘　　要：【目的】考察小檗碱及其亲脂性衍生物对大鼠C6胶质瘤细胞增殖、迁移与侵袭的影响。【方法】合成四种小檗碱衍生物9-O-十二烷基小檗碱(B3)、9-O-十六烷基小檗碱(B4)、9-O-十八烷基小檗碱(B5)、9-O-苄基小檗碱(B6)。采用1H NMR、13C NMR及ESI-MS确证其结构。四唑盐(MTT)比色法检测化合物在不同浓度下作用24、48、72 h后对C6细胞增殖活性的影响;细胞划痕实验和transwell迁移实验检测对细胞迁移能力的影响,transwell侵袭实验检测对细胞侵袭能力的影响。【结果】MTT结果显示,衍生物抑制细胞增殖作用显著强于对照组与小檗碱组(P<0.05);其中,B3的抑制作用最强。划痕实验、transwell迁移与侵袭实验结果显示,与对照组比较,小檗碱及其衍生物能明显抑制C6细胞的迁移与侵袭(P<0.05);其中,B3与B4抑制作用最强。【结论】小檗碱的亲脂性衍生物能有效地抑制C6胶质瘤细胞的增殖、迁移与侵袭,为开发新的恶性胶质瘤治疗方法提供新的思路。[ Objective] To evaluate the effect of berberine and its lipophilic derivatives on proliferation, migration and invasion of rat C6 glioma cells. [ Methods ] Four berberine derivatives, 9-O-dodecyl-berberine （B3）, 9-O-cetyl-berberine （B4）, 9-O-octadecyl- berberine （B5）, and 9-O-benzyl-berberine （B6） were synthesized and confirmed by IH NMR, 13C NMR, and ESI-MS. The effect of the derivatives at various concentrations on proliferative capability of C6 cells was detected by MTI＂ method after treated for 24 h, 48 h, and 72 h. Effect on migrating capability was evaluated with the wound scratch and transwell migration assays. Effect on invasiveness was investigated with transwell invasion assays. [ Results ] Compared with the control and berberine itself, berberine derivatives could significantly inhibit the proliferation of C6 glioma cells （P 〈 0.05）, among which B3 shows the strongest action. Compared with the control, both berberine and its derivatives could obviously suppress the migration and invasion of C6 cells~ supported by wound- scratch, transwell migration and invasion assays （P 〈 0.05）, among which B3 and B4 are the strongest ones. [ Conclusion ] Lipophilic berberine derivatives could effectively restrain the proliferation, migration and invasion of C6 glioma cells, which provided a novel strategy for the malignant glioma therapy.

关 键 词：小檗碱 恶性胶质瘤 迁移 侵袭 增殖 

分 类 号：R73[医药卫生—肿瘤]