期刊文献+
任意字段
题名或关键词
题名
关键词
文摘
作者
第一作者
机构
刊名
分类号
参考文献
作者简介
基金资助
栏目信息

抑制葡萄糖调节蛋白78表达对阿霉素诱导人乳腺癌SK-BR-3细胞凋亡的增敏作用 被引量：1

Inhibition of glucose regulated protein 78 in sensitizing adriamycin-induced apoptosis of human breast cancer cells
暂未订购
导出
摘要 目的:探讨特异性下调葡萄糖调节蛋白78(GRP78)对阿霉素(adriamyc in,ADR)诱导人乳腺癌SK-BR-3细胞凋亡的影响,以期为乳腺癌化疗提供新的靶点。方法:培养人乳腺癌SK-BR-3细胞,用ADR(1 mg/L)处理人乳腺癌SK-BR-3细胞0、6、12、24、36 h,W estern b lot检测GRP78的表达;ADR处理SK-BR-3细胞48 h后,用溴化丙啶染色测定细胞凋亡率;用小分子干扰RNA siRNA预处理SK-BR-3细胞,再予ADR同上处理,检测细胞凋亡率,比较siRNA作用前后细胞凋亡率的变化。结果:ADR可诱导内质网应激,上调GRP78的表达,SK-BR-3细胞对ADR诱导的细胞凋亡率<30%;siRNA可明显阻断GRP78的表达,显著增加ADR诱导的细胞凋亡作用,凋亡率达到(62.30±0.88)%(P<0.01)。结论:抑制GRP78的表达可增强人乳腺癌SK-BR-3细胞对ADR经内质网应激途径诱导细胞凋亡的敏感性,促进肿瘤细胞的凋亡,增强其抗肿瘤作用。 Objective：To study the effect of down-regulating glucose regulated protein 78（GRP 78） on adriamycin（ADR） induced apoptosis in human breast cancer cell line SK-BR-3,and to provide a new target for chemotherapy of breast cancer.Methods：Human breast cancer cell line SK-BR-3 cells were cultured,and treated with ADR（1 mg/L） for 0,6,12,24,and 36 hours;the expression of GRP78 at different time points was measured by Western blot.After treated with ADR for 48 hours,SK-BR-3 cells were harvest and stained with propidium iodide for apoptotic assay.SK-BR-3 cells were pretreated with siRNA,and the same was done to ADR;cell apoptosis was measured to compare the effect of GRP78 on ADR induced apoptosis in SK-BR-3.Results：ADR induced ER stress and up-regulated the expression of GRP78.ADR induced less than 30% cell apoptosis in SK-BR-3 cells.siRNA significantly blocked the expression of GRP78 and increased the apoptosis induced by ADR.The apoptosis rate was（62.30±0.88）%（P0.01）.Conclusions：Inhibition of the expression of GRP78 in human breast cancer cells SK-BR-3 can increase the sensitivity of ADR-induced apoptosis through ER pathway,which may promote the apoptosis of tumor cells and enhance the anti-tumor effect.
作者 刘宏莉 龚萍 刘浩 张旭东 蒋志文
机构地区 蚌埠医学院药学系安徽省生代药物工程技术研究中心
出处 《蚌埠医学院学报》 CAS 2010年第6期555-557,561,共4页 Journal of Bengbu Medical College
基金 安徽省人才开发基金资助项目(2002Z023) 安徽省自然科学基金资助项目(090413135) 安徽省高等学校优秀青年人才基金资助项目(2009SQRZ134ZD)
关键词 乳腺肿瘤 葡萄糖调节蛋白78 SK-BR-3细胞株 细胞凋亡 RNA 小分子干扰 breast cancer SK-BR-3 cell line glucose regulated protein 78 apoptosis RNA sall interfering
分类号 R737.9 [医药卫生—肿瘤]
  • 相关文献

参考文献11

  • 1Ortiz C, Cardemil L. Heat-shock response in two leguminous plants: a comparative study [J]. Exp Bot, 2001, 52 ( 361 ) : 1711 -1719.
  • 2Arap MA, Lahdenranta J, Mintz PJ, et al. Cell surface expression of the stress response chaperone GRP78 enables tumor targeting by circulating ligands [ J ]. Cancer Cell ,2004,6 (3) :275 -284.
  • 3Lee AS. GRP78 induction in cancer: therapeutic and prognostic implications[J].Cancer Res, 2007,67 ( 8 ) :3496 - 3499.
  • 4Gazit G, Lu J, Lee AS. Deregulation of GRP stress protein expression in human breast cancer cell lines [ J ]. Breast Cancer Res Treat, 1999,54 (2) : 135 - 146.
  • 5Fernandez PM, Tabbara SO, Jacobs LK, et al. Overexpression of the glucose-regulated stress gene GRP78 in malignant but not benign human breast lesions [ J ]. Breast Cancer Res Treat,2000, 59(1) :15 -26.
  • 6Jamora C, Dennert G, Lee AS. Inhibition of tumor progression by suppression of stress protein GRP78/Bip induction in fibrosarcoma B/C 10ME[J]. Proc Nayl Acad Sci U S A, 1996,93 ( 15 ) :7690 - 7694.
  • 7Xing X, Lai M, Wang Y, et al. Overexpression of glucose- regulated protein78 in colon cancer [ J ]. Clin Chim Acta, 2006, 364(1/2) :308 -315.
  • 8Tchounwou PB, Wilson BA, Ishaque AB, et al. Atrazine potentiation of arsenic trioxide-induced cytotoxicity and gene expression in human liver carcinoma cells ( HepG2 ) [J]. Mol Cell Bioehem, 2001 , 222 (112) :49 -59.
  • 9Zhou Y, Lee AS. Mechanism for the supperssion of the mammalian stress response by genidtein, an anticancer phytoestrogen from soy [J].Natl Cancer lnst, 1998,90(5 ) :381 - 388.
  • 10Reddy RK, Lu J, Lee AS. The endoplasmic reticulum chaperone glycoprotein GRP94 with Ca2 + -binding and antiapoptotic proterties is a novel proteolytic target of calpain during etoposide- induced apoptosis [ J ]. Biol chem, 1999, 274 ( 40 ) : 28476 - 28483.

二级参考文献35

  • 1[1]Haas IG. Bip(GRP78), an essential hsp 70 resident protein in the endoplasmic reticulum. Experiment, 1994;50(11,12):1012～20
  • 2[2]Witzmann FA, Jamot BM, Parker DN, Clack JW. Modification of hepatic immunoglobulin heavy chain binding protein(Bip/Grp78)following exposure to structurally diverse peroxisome proliferation. Fundam Appl Toxicol, 1994;23(1):1～8
  • 3[3]Li WW, Sistonen L, Morimoto RL, Lee AS. Stress induction of the mammalian GRP78/Bip protein gene: in vivo genomic footprinting and identification of p70 core from human nuclear extract as a DNA-binding component specific to the stress regulatory element. Mol Cell Biol, 1994;14(8):5533～46
  • 4[4]Ng DT, Watowich SS, Lamb RA. Analysis in vivo of GRP78-Bip/substrate interactions and their role in induction of the GRP78-Bip gene. Mol Biol Cell, 1992;3(2):143～55
  • 5[5]Xu A, Bellamy AR, Taylor JA. Bip(GRP78) and endoplasmin(GRP94) are induced following rotavirus infection and bind transiently to an endoplasmic reticulum-localized virion component. J Virol, 1998;72(12):9865～72
  • 6[6]Jorgensen MM, Jensen ON, Holst HU et al. GRP78 is involved in retention of mutant low density lipoprotein receptor protein in the endoplasmic reticulum. J Biol Chem, 2000;275(43):33861～8
  • 7[7]Miskovic D, Saiyer-Cid L, Ohan N et al. Isolation and characterization of a cDNA encoding a xenopus immunoglobulin binding protein, Bip(grp78). Comp Biochem Physiol B Biochem Mol Biol, 1997;116(2):227～34
  • 8[8]Techel D, Hafker T, Muschner S et al. Molecular analysis of a glucose-regulated gene(grp78) of neurospora carssa. Biochem Biophys Acta, 1998;1397(1):21～6
  • 9[9]Baqui MM, Gereben B, Harney JW et al. Distinct subcellular localization of transiently expresses type 1 and 2 iodothyronine deiodinasese as determined by immunofluorescence confocal microscopy. Endocrinology, 2000;141(11):4309～12
  • 10[10]Mkrtchian S, Fang C, Hellman U, Ingelman-Sundberg M. A stress-inducible ratliver endoplasmic reticulum protein, Erp29. Eur J Biochem, 1998;251(1-2):304～13

共引文献12

同被引文献7

引证文献1

蚌埠医学院学报
2010年 第6期

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部