目的探讨联氨基姜黄素(hydrazinocurcumin,HC)脂质体纳米颗粒(NPs)对人乳腺癌细胞株MDA-MB-231增殖、凋亡、侵袭及迁移的影响。方法通过薄膜分散-超声法制备联氨基姜黄素脂质体纳米颗粒(HC-NPs)。用HC-NPs处理细胞后,MTT法检测细胞增殖,刘氏染色法检测细胞形态学改变,流式细胞术检测细胞周期与凋亡,Transwell检测细胞的侵袭和迁移,Western blotting检测与细胞周期、凋亡、侵袭及迁移相关蛋白分子的变化。结果 HC-NPs可抑制MDA-MB-231细胞的增殖,使细胞形态变圆,诱导细胞发生G₂/M期阻滞,使细胞凋亡率明显增加(P<0.01),抑制细胞的侵袭和迁移。HC-NPs可下调磷酸化-信号转导和转录激活因子(p-STAT3)以及下游分子Cyclin D1、Survivin、Bcl-2及MMP-9的表达,上调Bax的表达。结论 HC-NPs可能通过抑制STAT3的激活,抑制细胞增殖、侵袭和迁移,促进细胞凋亡。

Objective To investigate the effects of liposome nanoparticles of hydrazinocurcumin(HC-NPs) on cells proliferation,apoptosis,invasion,and migration in human breast cancer MDA-MB-231 cells.Methods Liposome HC-NPs were prepared by film-sonication method and then were used to treat human breast cancer MDA-MB-231 cells.The treated cell survival was analyzed by MTT;Morphological changes were detected by Liu staining;The cell cycle and apoptosis were investigated by FCM assay;Then invasion and migration of the cells were analyzed by Transwell.Moreover,the expression of proteins correlated to cell cycle arrest,apoptosis,invasion,and migration were detected by Western blotting.Results The cell proliferation was inhibited by HC-NPs,the cells became round in shape,and the cells were arrested in G2/M phase,the ratio of apoptosis was increased(P0.01),the cells invasion and migration were restrained.The expression of p-STAT3,CyclinD1,Survivin,Bcl-2,and MMP-9 were down-regulated,while the expression of Bax was up-regulated.Conclusion The effects of HC-NPs on the suppression of cell proliferation,invasion,and migration,and induction of cells apoptosis may be related to the inhibition of STAT3 activation.

国家自然科学基金资助项目(NSFC30971131);重庆市科委自然科学基金资助项目(2009BB5077)