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目的探讨呫吨酮并吡啶衍生物5,9-二(2-吡咯烷基乙酰氨基)-7H-吡啶并[4,3-c]呫吨-7-酮(XP-16)抗人胃癌MGC-803细胞作用及其可能作用机制。方法通过MTT法、细胞形态学和克隆实验观察XP-16对MGC-803细胞增殖;应用Hoechest33258和PI双染法观察细胞凋亡;采用荧光分光光度计检测细胞内钙([Ca2+]i)及线粒体膜电位;RT-PCR检测Bad和金属硫蛋白1A(MT-1A)mRNA的表达。结果 XP-16能抑制MGC-803细胞增殖,呈浓度(r=0.88,P<0.01)和时间(r=0.93,P<0.05)依赖性。XP-16作用MGC-803细胞24 h后,MGC-803细胞出现染色质聚集、核碎裂等典型的凋亡形态学改变,且随XP-16浓度的增加,MGC-803细胞凋亡百分率逐渐增大。XP-16作用后,MGC-803细胞的[Ca2+]i和线粒体膜电位降低、Bad和MT-1A mRNA表达增加。结论 XP-16可通过诱导细胞凋亡抑制MGC-803细胞增殖,其机制可能与其降低[Ca2+]i和线粒体膜电位有关,而细胞内MT-1A表达的上调可能是[Ca2+]i下降的结果。
OBJECTIVE To investigate the anti-human gastric cancer MGC activity of Xanthoxypyridine derivative 5,9-bis (2-pyrrolidinylacetamido) -7H-pyrido [4,3-c] -803 cells and its possible mechanism. Methods The proliferation of MGC-803 cells was observed by MTT, cell morphology and cloning experiments. The apoptosis of MGC-803 cells was observed by Hoechest 33258 and PI double staining. The intracellular calcium ([Ca2 +] i) Mitochondrial membrane potential; Bad and expression of Bad metallothionein 1A (MT-1A) mRNA were detected by RT-PCR. Results XP-16 could inhibit the proliferation of MGC-803 cells in a dose-dependent manner (r = 0.88, P <0.01) and time (r = 0.93, P <0.05). The apoptosis of MGC-803 cells induced by XP-16 in MGC-803 cells for 24 h showed typical apoptosis morphological changes, such as chromatin accumulation and nuclear fragmentation. The apoptotic percentage of MGC-803 cells gradually increased with the increase of XP-16 concentration Increase. After treated with XP-16, the [Ca2 +] i and mitochondrial membrane potential of MGC-803 cells decreased and the expression of Bad and MT-1A mRNA increased. Conclusion XP-16 can inhibit the proliferation of MGC-803 cells by inducing apoptosis, which may be related to the decrease of [Ca2 +] i and mitochondrial membrane potential. The up-regulation of MT-1A expression may be the result of the decrease of [Ca2 +] i .