[1]浦龙健,黄莹莹,李阳,等.siRNA沉默葡萄糖调节蛋白78可增强乳腺癌细胞对顺铂的敏感性[J].南方医科大学学报,2013,(01):44.
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siRNA沉默葡萄糖调节蛋白78可增强乳腺癌细胞对顺铂的敏感性()
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《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2013年01期
页码:
44
栏目:
出版日期:
2013-01-15

文章信息/Info

Title:
Small interfering RNA-mediated glucose-regulated protein 78 knockdown enhances chemosensitivity of breast cancer cells to cisplatin
作者:
浦龙健黄莹莹李阳徐锦程蒋琛琛刘浩蒋志文
关键词:
乳腺癌葡萄糖调节蛋白78小干扰RNA顺铂凋亡
Keywords:
breast cancer glucose-regulated protein 78 small interfering RNA cisplatin apoptosis
摘要:
:目的探讨siRNA沉默葡萄糖调节蛋白78(GRP78)增强顺铂对乳腺癌细胞凋亡的敏感性,以期为乳腺癌的临床治疗提供
新的靶点。方法MTT法检测不同浓度(0、1、2、4、8、16 μmol/L)顺铂对乳腺癌细胞MDA-MB-231的增殖抑制作用;PI/Annexin
V 双染检测顺铂(8 μmol/L)对siRNA转染沉默GRP78乳腺癌细胞MDA-MB-231凋亡的影响,同时将未转染和转染空质粒乳腺
癌细胞MDA-MB-231 作为空白和阴性对照;Western blot 检测顺铂(8 μmol/L)处理乳腺癌细胞MDA-MB-231 不同时间(0、6、
16、24 h)GRP78的表达以及siRNA转染沉默GRP78乳腺癌细胞MDA-MB-231 中GRP78的表达。结果8 μmol/L顺铂作用于
乳腺癌细胞MDA-MB-231 24、48、72 h细胞存活率分别为83.13%、54.22%、35.79%,但24 h细胞凋亡率仅为10.8%。将GRP78
沉默后,细胞的凋亡率为24.6%,沉默GRP78并合用顺铂进行刺激,细胞的凋亡率为48.9%,明显高于单用顺铂组。用顺铂刺激
乳腺癌细胞MDA-MB-231 GRP78表达先上调后有减弱趋势,而siRNA转染沉默GRP78后,GRP78表达明显下降。结论抑制
GRP78的表达可以增加乳腺癌细胞的凋亡率,为乳腺癌的临床治疗提供了新的靶点。
Abstract:
Objective To investigate the effect of small interfering RNA-mediated glucose-regulated protein 78 (GRP78)
knockdown on the chemosensitivity of breast cancer cells to cisplatin. Methods Human breast cancer cell line MDA-MB-231
was exposed to different doses of cisplatin (0, 1, 2, 4, 8, and 16 μmol/L), and the changes in cell viability were detected using
MTT assay. PI/Annexin V staining was used to observe the apoptosis of the cells in response to transfection with a small
interfering RNA targeting GRP78 (pSH1Si-GRP78). Western blotting was employed to detect GRP78 expression in pSH1Si-
GRP78-transfected cells after exposure to 8 μmol/L cisplatin for 24, 48 and 72 h. Results Exposure of the cells to 8 μmol/L
cisplatin for 24, 48 and 72 h resulted in a cell survival rate of 83.13%, 54.22% and 35.79%, respectively, but the cell apoptosis
rate was only 10.8% at 24 h. Transfection of MDA-MB-231 cells with pSH1Si-GRP78 caused a cell apoptosis rate of 24.6%,
which increased to 48.9% in cells with both pSH1Si-GRP78 transfection and cisplatin exposure. Cisplatin exposure caused an
initial up-regulation followed then by a down-regulation of GRP78 expression in MDA-MB-231 cells, while pSH1Si-GRP78
transfection produced an obvious down-regulation of GRP78 expression. Conclusions Inhibition of GRP78 expression
increases the apoptosis and enhance cisplatin chemosensitivity of breast cancer cells in vitro, suggesting the value of GRP78 as
a potential therapeutic target in the clinical treatment of breast cancer.

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更新日期/Last Update: 1900-01-01