3,4-二氯异香豆素对胃癌细胞Smad1和PTEN基因的影响-东南大学学报医学版

3,4-二氯异香豆素对胃癌细胞Smad1和PTEN基因的影响

单位：东南大学附属中大医院,肿瘤中心,江苏,南京,210009

分类号：Q253, R735.2

出版年·卷·期（页码）：2008·27·第三期（184-187）

摘要：

目的:探讨蛋白酶体抑制剂3,4-二氯异香豆素(DCI)对人胃癌细胞株BGC-823细胞Smad1及PTEN基因的影响.方法:MTT法检测DCI、5-FU单药及联合干预后BGC-823细胞的生存率,流式细胞术检测细胞凋亡率及周期分布状况,RT-PCR法检测Smad1和PTEN基因表达.结果:75 μmol·L-1 DCI干预24 h后,细胞生存率为(84.0±9.60)%,750 μmol·L-1DCI作用72 h后,细胞生存率仅有(20.3±9.7)%;同时,当DCI浓度从150 μmol·L-1上升至600 μmol·L-1时,细胞凋亡率相应地从15.0%增加至27.8%;DCI可以增强5-FU对胃癌细胞的杀伤作用;DCI浓度依赖性地上调Smad1和PTEN基因表达(P<0.05),当DCI浓度从150 μmol·L-1上升至600 μmol·L-1时,Smad1和PTEN基因分别从上调19.45%、6.16%升至上调72.85%、48.46%.结论:蛋白酶体抑制剂DCI可能通过干预骨形态发生蛋白(BMP)信号通路减少Smad1降解、增加PTEN表达,产生抗肿瘤效应.

Objective To investigate effects of 3,4-dichloroisocoumarin(DCI) on SMAD1 and PTEN in human gastric carcinoma cells lines-BGC-823,and combined effects of DCI and 5-fluorouracil(5-FU) on multiplication of BGC-823.Methods The survival rate of BGC-823 was detected with MTT colorimetry and the apoptosis and cell cycle of BGC-823 were analyzed with flow cytometry,RT-PCR was used to observe the change of expression of Smad1 and PTEN in BGC-823.Results The survival rate of the group treated with DCI at the dose of 75 μmol·L-1after 24 h,750 μmol·L–1 after 72 h was(84.0±9.6)% and(20.3±9.7)% respectively.The concentration of DCI was increased from 150 μmol·L-1 to 600 μmol·L-1,the apoptosis rate of BGC-823 cell line elevated from 15.0%to 27.8%.The combination of DCI and 5-FU enhanced the cytotoxic effect of 5-FU on BGC-823 cells(P<0.05).DCI up-regulates gene expression of Smad1 and PTEN in a concentration-dependent manner.When the concentration of DCI was increased from 150 μmol·L-1 to 600 μmol·L-1,the rate of upregulation of Smad1 and PTEN gene expression elevated from 19.45%,6.16% to 72.85%,48.46% accordingly.ConclusionProteasome inhibitor-DCI has an anticancer effect and can enhance the action of 5-FU through the pathway of interfering with BMP signal transduction pathways of gastric carcinoma cell to decrease the degradation of Smad1 and induce the expression of PTEN to increase.

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