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作 者:焦青[1] 邹莉波[1] 刘鹏[1] 迟天燕[1] 曹雪松[1] 邹璐[1]
机构地区:[1]沈阳药科大学生命科学与生物制药学院,辽宁沈阳110016
出 处:《沈阳药科大学学报》2013年第10期793-798,共6页Journal of Shenyang Pharmaceutical University
基 金:辽宁省教育厅科学技术研究项目(2010526);国家科技部"十一五"国家科技重大专项"重大新药创制"平台建设项目(2009ZX09301-012)
摘 要:目的观察文冠果壳苷对人恶性黑色素瘤A375.S2细胞增殖抑制作用及诱导凋亡的机理。方法采用四甲基噻唑蓝法(MTT法)检测化合物对细胞的生长抑制作用,光学显微镜及荧光显微镜观察细胞形态学变化,免疫印迹法(Western blotting)检测p-p38、p38、核转录因子-κB(nuclear factor kappa B,NF-κB)p65及核转录抑制因子-κB(nuclear factor kappa B inhibitor,I-κB)蛋白表达水平,检测细胞核内NF-κB p65表达水平。结果文冠果壳苷可浓度依赖性地抑制A375.S2细胞增殖,并优于5-氟尿嘧啶(5-FU);10μmol·L-1文冠果壳苷作用于A375.S2细胞,形态学观察发现明显的凋亡小体和核固缩;Western blotting检测发现文冠果壳苷可时间依赖性地降低p-p38、p38、NF-κB p65及I-κB的蛋白表达水平;文冠果壳苷抑制NF-κB p65自细胞浆到细胞核的转位。结论文冠果壳苷可能通过抑制NF-κB和p38的活化诱导人恶性黑色素瘤A375.S2细胞凋亡。Objective To study the antitumor effect and mechanism of xanthoceraside on human melanoma A375. $2 cells. Methods The effect of xanthoceraside on the proliferation of A375. $2 cells was measured by MTT test. Morphological changes of tumor cells were analyzed by inverted microscope. Protein levels of p38 ,p-p38 ,I-KBo and NF-KB p65 and the effect of xanthoceraside on p65 translocation were analyzed by Western blotting. Results Xanthoceraside significantly inhibited the proliferation of A375. $2 cells in concen- tration-dependent manner. The apoptotic bodies were observed after the A375. $2 cells were exposed to xan- thoceraside. The protein levels of p38, p-p38, I-KBa and NF-KB p65 were decreased. Furthermore, xantho- ceraside inhibited the translocation of NF-KB p65 into the nucleus. Conclusions Xanthoceraside can induce apoptosis with downregulation of p38 and inhibition of NF-KB activity in human melanoma cancer cells A375. S2.
关 键 词:文冠果壳苷 人恶性黑色素瘤A375.S2细胞 细胞凋亡 P38 NF-ΚB
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