兰州大学机构库 >学院待认领
鬼臼酰肼哌啶氮氧自由基腙(GP1)抑制胃癌细胞生长及血管生成因子表达的实验研究
Alternative TitleEffects of Podophyllic Acid Piperdyl Nitroxyl Radical Hydrazine on Gastric Cancer Cells and Angiogenesis Factor
赵苗苗
Thesis Advisor陈晓
2014-05-22
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name硕士
Keyword鬼臼酰肼哌啶氮氧自由基腙 抗血管生成 抗肿瘤
Abstract目的: 研究GP1抑制胃癌细胞增殖及抗血管生成作用的机理,为探讨GP1的抗肿瘤作用提供分子机制和理论依据,提供进一步研发抗肿瘤新药的理论基础。 方法:选用BGC-823、MKN-45为模型,采用Cell Counting Kit-8试剂盒测定不同浓度、不同时间点的GP1对细胞生长的影响;选用100ug/mL的GP1作用胃癌细胞24h、48h,用流式细胞仪检测细胞凋亡;Transwell小室法检测GP1作用细胞24h、48h,对细胞迁移的影响;选用200、100、50ug/mL的GP1作用细胞用RT-PCR测定VEGF-A、VEGFR、Ang-1、Tie2、MMP-2、9mRNA的表达的影响。 结果:1 GP1浓度为100ug/mL作用24、48、72hBGC-823的抑制率依次为:31.31%、36.69%、39.23%,MKN-45的抑制率依次为64.38%、73.16%、80.32%。2 GP1作用后凋亡率随着药物作用时间的延长而增高。BGC-823 24、48h的凋亡率分别为0.0800±0.1000﹪、0.1667±0.01528﹪;MKN-45凋亡率分别为0.0733±0.02082﹪、0.2767±0.01202﹪。3 Transwell小室法检测GP1作用24、48h均抑制BGC-823、MKN-45细胞的迁移;GP1作用于24、48h后BGC-823细胞的抑制迁移率分别为:,MKN-45细胞的抑制迁移率分别为17.29%,24.28%。4 GP1能够抑制血管生成因子VEGF-A、VEGFR、Ang-1、Tie2及MMP-2、9mRNA的表达。    结论:GP1对在体外生长的胃癌细胞有明显的抑制作用,且可能是通过诱导胃癌细胞凋亡而抑制其增殖;GP1可能是通过抑制胃癌细胞MMP-2、MMP-9 MRNA的表达来抑制其迁移;GP1具有抑制VEGF-A、VEGFR、Ang-1、Tie2 MRNA表达的作用,GP1可能具有抑制胃癌血管生成的作用。
Other AbstractObjectives: To study stable nitroxyl radicals spin-labeled podophyllotoxin derivatives- podophyllic acid piperdyl nitroxyl radical hydrazine(GP1) inhibit activities of gastric cancer cells BGC-823、MKN-45 in vitro and the mechanism of anti-angiogenesis,providing molecular mechanism and the theoretical basis for further research and development of anti-tumor drugs. Methods: CCK-8 assay was used to observe the inhibition rate of gastric carcinoma cells in different concentrations and different time points.The apoptosis were examined through FCM.The invasiveness was examined in Transwell chamber; RT-PCR was used to detect the expressions of VEGF-A、VEGFR、Ang-1、Tie2、MMP-2、MMP-9 mRNA in the cell lines. Results: 1.GP1 have the inhibitory effect and the most obvious inhibition when the concentration of it was 100μg·mL-1. The inhibition rate of GP1 in 100μg·mL-1 on gastric carcinoma BGC-823 24h、48h、72h were 31.31%, 36.69%, 39.23%respectively;on gastri carcinoma MKN-45 24h、48h、72hwere 64.38%, 73.16%, 80.32%respectively;2.GP1 can induce gastric cancer cell apoptosis,effect increasing the effect with the time.The apoptosis rate of GP1 in 100μg·mL-1 on gastric carcinoma BGC-823 24h、48h were 0.0800±0.1000﹪、0.1667±0.01528﹪;gastric carcinoma MKN-45 24h、48h were 0.0733±0.02082﹪、0.2767±0.01202﹪。3.GP1 can inhibit gastric cancer cell migration.The migration rate of GP1 in 100μg·mL-1 on gastric carcinoma BGC-823 24h、48h were 18.85%、25.15%;gastric carcinoma MKN-45 24h、48h were 17.29%、24.28%。4.GP1 in 200、100、50μg·mL-1were inhibited the expression of VEGF-A、VEGFR、Ang-1、Tie2、MMP-2、MMP-9mRNA. Conclusions: GP1 has inhibitory effect on gastric carcinoma cells in vitro by apoptosis-inducing.GP1 may inhibit migration of gastric carcinoma cells by inhibiting expression of MMP-2、MMP-9、MRNA. GP1 may inhibit angiogenesis of gastric carcinoma cells by inhibiting expression of VEGF-A、VEGFR、Ang-1、Tie2MRNA.
URL查看原文
Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/223356
Collection学院待认领
Affiliation临床医学院
Recommended Citation
GB/T 7714
赵苗苗. 鬼臼酰肼哌啶氮氧自由基腙(GP1)抑制胃癌细胞生长及血管生成因子表达的实验研究[D]. 兰州. 兰州大学,2014.
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