A proteomic investigation into adriamycin chemo-resistance of human leukemia K562 cells

This study aimed to explore the mechanism of adriamycin resistance in human chronic myelogenous leukemia cells. Proteomic approach was utilized to compare and identify differentially expressed proteins between human chronic myelogenous leukemia K562 cells and their adriamycin-resistant counterparts. The differentially expressed proteins were analyzed by 2-DE (two-dimensional gel electrophoresis), and protein identification were performed on ESI-Q-TOF MS/MS instrument. Out of the 35 differentially expressed proteins between the two cell lines, 29 were identified and grouped into 10 functional classes. Most of identified proteins were related to the categories of metabolism (24%), proteolysis (13%), signal transduction (21%) and calcium ion binding (6%), suggesting that alterations of those biological processes might be involved in adriamycin resistance of K562 cells. We believe this study may provide some clues to a better understanding of the molecular mechanisms underlying adriamycin resistance.

[1]  Enhanced expression of Annexin A4 in clear cell carcinoma of the ovary and its association with chemoresistance to carboplatin , 2009, International journal of cancer.

[2]  Zhuchu Chen,et al.  Increased expression of HSP27 linked to vincristine resistance in human gastric cancer cell line , 2009, Journal of Cancer Research and Clinical Oncology.

[3]  R. Callaghan,et al.  Inhibition of P-glycoprotein function by XR9576 in a solid tumour model can restore anticancer drug efficacy. , 2004, European journal of cancer.

[4]  P. Sinha,et al.  Proteomics for studying cancer cells and the development of chemoresistance , 2001, Proteomics.

[5]  D. Fan,et al.  Regulation of drug sensitivity of gastric cancer cells by human calcyclin-binding protein (CacyBP) , 2004, Gastric Cancer.

[6]  T. Sasaki,et al.  The Rho small G protein family-Rho GDI system as a temporal and spatial determinant for cytoskeletal control. , 1998, Biochemical and biophysical research communications.

[7]  C. Dermardirossian,et al.  Structure-activity relationships in flexible protein domains: regulation of rho GTPases by RhoGDI and D4 GDI. , 2001, Journal of molecular biology.

[8]  L. Guijarro,et al.  Protein kinase C isozymes in prostatic epithelial cells from normal, diabetic and insulin-treated diabetic rats. , 1995, General pharmacology.

[9]  L. Tanoue.  Cancer Statistics, 2009 , 2010 .

[10]  S. Prost.  Mechanisms of resistance to topoisomerases poisons. , 1995, General pharmacology.

[11]  A. López-Rivas,et al.  The differential sensitivity of Bc1-2-overexpressing human breast tumor cells to TRAIL or doxorubicin-induced apoptosis is dependent on Bc1-2 protein levels , 2001, Oncogene.

[12]  B. Olofsson,et al.  Rho guanine dissociation inhibitors: pivotal molecules in cellular signalling. , 1999, Cellular signalling.

[13]  U. Mazurek,et al.  The hypoxic cell a target for selective cancer therapy , 2009 .

[14]  D. Schadendorf,et al.  Study of the development of chemoresistance in melanoma cell lines using proteome analysis , 2003, Electrophoresis.

[15]  E. Dees,et al.  The proteasome as a target for cancer therapy. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[16]  M. J. van de Vijver,et al.  Expression of the breast cancer resistance protein in breast cancer. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[17]  Yves Pommier,et al.  Apoptosis defects and chemotherapy resistance: molecular interaction maps and networks , 2004, Oncogene.

[18]  P. V. van Diest,et al.  Levels of hypoxia‐inducible factor‐1α independently predict prognosis in patients with lymph node negative breast carcinoma , 2003, Cancer.

[19]  A. Jemal,et al.  Cancer Statistics, 2009 , 2009, CA: a cancer journal for clinicians.

[20]  Y. Yang,et al.  Anxa2 plays a critical role in enhanced invasiveness of the multidrug resistant human breast cancer cells. , 2009, Journal of proteome research.

[21]  D. Schadendorf,et al.  Study of Therapy Resistance in Cancer Cells with Functional Proteome Analysis , 2002, Clinical chemistry and laboratory medicine.

[22]  Ruedi Aebersold,et al.  Proteomic Profiling of Pancreatic Cancer for Biomarker Discovery* , 2005, Molecular & Cellular Proteomics.

[23]  K. Kaibuchi,et al.  Molecular cloning and characterization of a novel type of regulatory protein (GDI) for the rho proteins, ras p21-like small GTP-binding proteins. , 1990, Oncogene.

[24]  Eithne Costello,et al.  Proteomic technologies and their application to pancreatic cancer , 2004, Expert review of proteomics.

[25]  Baolin Zhang,et al.  Rho GDP dissociation inhibitor protects cancer cells against drug-induced apoptosis. , 2005, Cancer research.

[26]  Yuquan Wei,et al.  Proteomic analysis of liver cancer cells treated with suberonylanilide hydroxamic acid , 2008, Cancer Chemotherapy and Pharmacology.

[27]  B. Teicher.  Hypoxia and drug resistance , 1994, Cancer and Metastasis Reviews.

[28]  P. Vaupel,et al.  Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. , 2001, Journal of the National Cancer Institute.

[29]  F. Caponigro,et al.  The proteasome: a worthwhile target for the treatment of solid tumours? , 2007, European journal of cancer.

[30]  J. Adams.  The proteasome: a suitable antineoplastic target , 2004, Nature Reviews Cancer.

[31]  D. Schadendorf,et al.  Identification of novel proteins associated with the development of chemoresistance in malignant melanoma using two‐dimensional electrophoresis , 2000, Electrophoresis.

[32]  H. Friess,et al.  Application of laser capture microdissection combined with two‐dimensional electrophoresis for the discovery of differentially regulated proteins in pancreatic ductal adenocarcinoma , 2003, Proteomics.

[33]  T. Maniatis,et al.  A ubiquitin ligase complex essential for the NF-kappaB, Wnt/Wingless, and Hedgehog signaling pathways. , 1999, Genes & development.

[34]  E. Monti,et al.  Molecular determinants of intrinsic resistance to doxorubicin in human cancer cell lines. , 2003, International journal of oncology.

[35]  M. Borad,et al.  The proteasome inhibitor PS-341 markedly enhances sensitivity of multiple myeloma tumor cells to chemotherapeutic agents. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[36]  Ruedi Aebersold,et al.  Pancreatic cancer proteome: the proteins that underlie invasion, metastasis, and immunologic escape. , 2005, Gastroenterology.

[37]  M. Henry,et al.  Proteomic investigation of taxol and taxotere resistance and invasiveness in a squamous lung carcinoma cell line. , 2008, Biochimica et biophysica acta.

[38]  S. Zeng,et al.  Involvement of annexin A1 in multidrug resistance of K562/ADR cells identified by the proteomic study. , 2009, Omics : a journal of integrative biology.

[39]  C. Koch,et al.  Prognostic significance of tumor oxygenation in humans. , 2003, Cancer letters.

[40]  Janice M. Y. Brown,et al.  The hypoxic cell: a target for selective cancer therapy--eighteenth Bruce F. Cain Memorial Award lecture. , 1999, Cancer research.