High expression of neuroguidin increases the sensitivity of acute myeloid leukemia cells to chemotherapeutic drugs

Journal of Hematology & Oncology

Jianmin Wang¹  Hong Zhou¹  Min Liu¹  Gusheng Tang¹  Hui Cheng¹  Shuqing Lü¹  Kejun Chen¹ 

[1] Department of Hematology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China

关键词: mTOR;    Chemotherapeutic drug;    Multidrug-resistant;    Acute myeloid leukemia;    Neuroguidin;   

Others  :  1133365
DOI  :  10.1186/s13045-015-0108-6

 received in 2014-12-17, accepted in 2015-01-08,  发布年份 2015

【 摘 要 】

Neuroguidin (NGDN) is a eukaryotic translation initiation factor 4E binding protein. The purpose of this study was to clarify the function of NGDN and its possible mechanism of action in human myeloid leukemia cells. Proliferation inhibition and apoptosis in NGDN over-expressing myeloid multidrug-resistant leukemia cells (K562/A02-NGDN) was significantly higher than in control K562/A02 cells following treatment with vincristine, etoposide, and epirubicin, indicating that NGDN over-expression can increase the sensitivity of multidrug-resistant leukemia cells to chemotherapeutic drugs. Furthermore, NGDN knock-down in K562/A02 cells resulted in the activation of multiple tumor-related signaling pathways, especially the mammalian target of rapamycin (mTOR) pathway.

【 授权许可】

   
2015 Chen et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Lü SQ, Xu XP, Xia F, Wang JM: Differential gene expression analysis of human leukemic cell line with different tumorigenic potentials in nude mice. Zhonghua Zhong Liu Za Zhi 2004, 26:196-200.
• [2]Chen L, Xu XP, Wang JM, Li Y, Xu H, Lü SQ, et al.: Spectrum of gene expression of a multi-drug resistant leukemia cell line with high tumorigenicity in nude mice. Zhonghua Zhong Liu Za Zhi 2005, 27:196-200.
• [3]Chen L, Wang JM, Xu XP, Li Y, Xu H, Ju XP, et al.: A pilot study of spectrum of gene expression of acute leukemia. Zhonghua Yi Xue Za Zhi 2005, 85:1089-92.
• [4]Jung MY, Lorenz L, Richter JD: Translational control by neuroguidin, a eukaryotic initiation factor 4E and CPEB binding protein. Mol Cell Biol 2006, 26:4277-87.
• [5]Richter JD, Sonenberg N: Regulation of cap-dependent translation by eIF4E inhibitory proteins. Nature 2005, 433:477-80.
• [6]Dilling MB, Germain GS, Dudkin L, Jayaraman AL, Zhang X, Harwood FC, et al.: 4E-binding proteins, the suppressors of eukaryotic initiation factor 4E, are down-regulated in cells with acquired or intrinsic resistance to rapamycin. J Biol Chem 2002, 277:13907-17.
• [7]Provenzani A, Fronza R, Loreni F, Pascale A, Amadio M, Quattrone A: Global alterations in mRNA polysomal recruitment in a cell model of colorectal cancer progression to metastasis. Carcinogenesis 2006, 27:1323-33.
• [8]Coleman LJ, Peter MB, Teall TJ, Brannan RA, Hanby AM, Honarpisheh H, et al.: Combined analysis of eIF4E and 4E-binding protein expression predicts breast cancer survival and estimates eIF4E activity. Br J Cancer 2009, 100:1393-9.
• [9]Yuan R, Kay A, Berg WJ, Lebwohl D: Targeting tumorigenesis: development and use of mTOR inhibitors in cancer therapy. J Hematol Oncol 2009, 2:45. BioMed Central Full Text
• [10]Castellvi J, Garcia A, Rojo F, Ruiz-Marcellan C, Gil A, Baselga J, et al.: Phosphorylated 4E binding protein 1: a hallmark of cell signaling that correlates with survival in ovarian cancer. Cancer 2006, 107:1801-11.
• [11]Clemens MJ, Elia A, Morley SJ: Requirement for the binding proteins for the synergistic down-regulation of protein synthesis by hypertonic conditions and mTOR inhibition. PLoS ONE 2013, 8:e71138.
• [12]Chakravarthy R, Clemens MJ, Pirianov G, Perdios N, Mudan S, Cartwright JE, et al.: Role of the eIF4E binding protein 4E-BP1 in regulation of the sensitivity of human pancreatic cancer cells to TRAIL and celastrol-induced apoptosis. Biol Cell 2013, 105(9):414-29.
• [13]Zhu HL, Xie SM, Fang M, Zhang JJ, Weng ZP, Zhong XY: 4E-BP1 regulates the sensitivity of human glioma cells to chemotherapy through PI3K/Akt/mTOR-independent pathway. Neuropathology 2014, 34(3):227-35.
• [14]Sun SY, Rosenberg LM, Wang X, Zhou Z, Yue P, Fu H, et al.: Activation of Akt and eIF4E survival pathways by rapamycin-mediated mammalian target of rapamycin inhibition. Cancer Res 2005, 65(16):7052-8.