|Table of Contents|

The change and effect of Beclin 1 on cytotoxicity of ovarian cancer cells induced by MG132

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2014 01
Page:
4-0007
Research Field:
Publishing date:

Info

Title:
The change and effect of Beclin 1 on cytotoxicity of ovarian cancer cells induced by MG132
Author(s):
Liu Chuan1; Hu Zhenhua1; Tan Mingzi1; Liu Baoqin2; Ying Tianshu1; Lin Bei1
1.Department of Obstetrics and Gynecology,Shengjing Hospital Affiliated to China Medical University,Liaoning Shenyang 110004,China;2.Department of Biochemistry and Molecular Biology,China Medical University,Liaoning Shenyang 110001,China.
Keywords:
proteasome inhibitor; autophagy; apoptosis; Beclin 1; ovarian cancer
PACS:
R73-36+2;R737.31
DOI:
10.3969/j.issn.1672-4992.2014.01.02
Abstract:
Objective:To investigate the change and the effect of Beclin 1 on cytotoxicity of ovarian cancer cells mediated by proteasome inhibitor MG132.Methods:OVCAR3 cells were treated with indicated concentrations of proteasome inhibitor MG132 for 24h,cell viability was measured using MTT assay and beclin 1 expression was detected using Western blot.OVCAR3 cells were transfected with mock or Beclin 1 eukaryotic plasmid,then treated with MG132,cell viability was measured using MTT assay; Nuclear morphology was analyzed using Hoechst 33258 staining.OVCAR3 cells were transfected with Beclin 1 specific shRNA（shBeclin 1）,then treated with MG132 for 24h,the formation of acidic vacuoles were analyzed using AO staining.Results:1,2,5,10 μmol/L MG132 resulted in suppression of cell growth(P＜0.05)；5μmol/L and 10μmol/L MG132 reduced Beclin 1 expression at the protein levels in OVCAR3 cells(both P=0.001).Overexpression of Beclin 1 enhanced the cytotoxicity of OVCAR3 cells mediated by MG132(P=0.00089),and apoptotic morphological characteristics turned more predominant.Downregulation of Beclin 1 by shRNA demonstrated no obvious effect on accumulation of acidic vesicular organelles induced by MG132.Conclusion:MG132 reduced the Beclin 1 level in OVCAR3 cells,Beclin 1 enhanced the cytotoxicity of OVCAR3 cells mediated by MG132 in an autophagy-independent manner.

References:

［1］Liang XH,Jackson S,Seaman M,et al.Induction of autophagy and inhibition of tumorigenesis by beclin 1［J］.Nature,1999,402(6762):672-676.
［2］Kahana S,Finniss S,Cazacu S,et al.Proteasome inhibitors sensitize glioma cells and glioma stem cells to RTAI-induced apoptosis by PKC epsition-dependent downregulation of AKT and XIAP expressions［J］.Cellular Signalling,2011,23(8):1348-1357.
［3］Yoshiba S,Iwase M,Kurihara S,et al.Proteasome inhibitor sensitizes oral squamous cell carcinoma cells to TRAIL-mediated apoptosis［J］.Oncol Rep,2011,25(3):645-652.
［4］Zuo J,Bi CF,Fan YH,et al.Cellular and computational studies of proteasome inhibition and apoptosis induction in human cancer cells by amino acid Schiff base-copper complexes［J］.Apoptosis,2013,118:83-93.
［5］Kane RC,Bross PF,Frarell AT,et al.Velcade:USFDA approval for the treatment of multiple myeloma progressing on prior therapy［J］.Oncologist,2003,8(6):508-513.
［6］刘川、王华芹、高雁艳,等.MG132联合自噬抑制剂对A2870卵巢癌细胞抗肿瘤效应的研究［J］.中华肿瘤防治杂志,2013,20(3):161-165.
［7］Rikiishi H.Autophagic and apoptotic effects of HDAC inhibitors on cancer cells［J］.J Biomed Biotech,2011,83:260.
［8］Shao Y,Gao Z,Marks PA,et al.Apoptotic and autophagic cell death induced by histone deacetylase inhibitors［J］.Proc Natl Acad Sci USA,2004,101(52):18030- 18035.
［9］Park JH,Ahn MY,Kim TH,et al.A new synthetic HDAC inhibitor,MHY218,induces apoptosis or autophagy-related cell death in tamoxifen-resistant MCF-7 breast cancer cells［J］.Proc Natl Acad Sci USA,2012,30(5):1887-1898.
［10］Palumbo S,Pirtoli L,Tini P.Different involvement of autophagy in human malignant glioma cell lines undergoing irradiation and temozolomide combined treatments［J］.J Cell Biochem,2012,113(7):2308-2318.
［11］Brech A,Ahlquist T,Lothe RA,et al.A phosphatidylinositol 3-kinase class III sub-complex containing VPS15,VPS34,Beclin1,UVRAG and BIF-1 regulates cytokinesis and degradative endocytic traffic［J］.Exp Cell Res,2010,316(20):3368-3378.
［12］Liang XH,Kleeman LK,Jiang HH,et al.Protection againse fatal Sindbis virus encephalitis by Beclin 1,a novel Bcl-2-interacting protein［J］.J Virol,1998,72(11):8586-8596.
［13］Wang WY,Fan HK,Zhou Y,et al.Knockdown of autophagy-related gene BECLIN 1 promotes cell growth and inhibits apoptosis in the A549 human lung cancer cell line［J］.Mol Med Rep,2013,7(5):1501-1505.
［14］Song Jr,Guo XL,Xie XQ,et al.Autophagy in hypoxia protects cancer cells against apoptosis induced by nutrient deprivation through a Beclin 1-depentent way in hepatocellular carcinoma［J］.J Cell Biochem,2011,112(11):3406-3420.
［15］Nicotra G,Mercalli F,Peracchio C,et al.Autophagy-active Beclin-1 correlates with favourable clinical outcome in non-Hodgkin lymphomas［J］.Mod Pathol,2010,23(7):937-950.

Memo

Memo:
国家自然科学基金资助项目（编号：81172491）;高等学校博士学科点专项科研基金项目（编号：20112104110016）
Last Update: 2013-12-03