五没食子酰基葡萄糖抑制卵巢癌细胞增殖及其机制的分析-analysis of the inhibitory effect of pentagalloyl glucose on proliferation of ovarian cancer cells and its mechanism.docxVIP

广东药学院硕士研究生学位论文 广东药学院硕士研究生学位论文 inhibited NF-?B transcription activity. 4. RT-PCR was used to research the PGG- induced transcription alteration of NF-?B target genes, including bcl-2, bcl-xl, ciap-1, ciap-2, survivin, niap, xiap, cyclinD1, all were prosurvival genes in tumor cells. Results: 1．PGG inhibited proliferation of ovarian cancer HO-8910, HO-8910PM and SKOV-3 cells. The inhibitory effects appear a time-and –does dependent manner when the treatment exceeded 48 hours or the does of PGG exceeded 20μ M （P0.05）. 2．PGG treatment changed cell cycle distribution of three ovarian cancer HO-8910, HO-8910PM and SKOV-3 cells, and induced apoptosis in HO-8910, HO-8910PM , but not in SOV-3 cells. PGG induced S- phase enrichment in three ovarian cancer cells in a time-and –does dependent manner. The PGG- induced apoptosis- like change of nucleus was observed in HO-8910 and HO-8910PM, but not in SKOV-3 cells, all treated with PGG and then stained with Hoechst. The apoptosis induced by PGG was also confirmed by AnnexinV-FITC positive of HO-8910 and HO-8910PM cells, that indicates cell membrane eversion in apoptosis. 3． PGG treatment induced activated caspases of caspase firmly, that are c-Caspase-9, 3,7. The cleavage o f caspase-8 was inhibited by PGG treatment, though PGG up-regulated the upstream tumor necrosis factor receptor. 4． PGG treatment repressed nuclear translocation of P65 NF-?B and enriched I?B, the inhibitory protein， in cytoplasm. Accordingly，the mRNA of target genes of NF-?B， bcl-2， bcl-xl， surviving， niap， xiap， cyclinD1， but not ciap-1 or ciap-2, was down-regulated. PGG treatment had no effects on the mRNA expression of bax. Conclusion: Through inducing cell cycle retardation in cell cycle and apoptosis，PGG can inhibit proliferation of ovarian carcinoma cells. PGG could have repressed the transcription activity of oncogenic transcription factor NF-?B to down-regulate the expression of apoptosis- inhibitory genes, finally triggered endogenous caspas