Skip to main content

Advertisement

SpringerLink
Log in

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

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

2-DE:

Two-dimensional gel electrophoresis

ACN:

Acetonitrile

CBB:

Coomassie brilliant blue

DMEM:

Dulbecco-modified Eagle medium

IEF:

Isoelectric focusing

IPG:

Immobilized pH gradient

MS:

Mass spectrometry

PBS:

Phosphate-buffered saline

PVDF:

Polyvinylidene fluoride

Q-TOF:

Quadrupole time-of-flight

TBST:

Tris-buffered saline Tween-20

References

  1. Jemal A, Siegel R, Ward E, Hao YP, Xu JQ, Thun MJ (2009) Cancer statistics, 2009. CA Cancer J Clin 59:225–249

    Article  PubMed  Google Scholar 

  2. Faneyte IF, Kristel PM, Maliepaard M et al (2002) Expression of the breast cancer resistance protein in breast cancer. Clin Cancer Res 8:1068–1074

    PubMed  CAS  Google Scholar 

  3. Walker J, Martin C, Callaghan R (2004) Inhibition of P-glycoprotein function by XR9576 in a solid tumour model can restore anticancer drug efficacy. Eur J Cancer 40:594–605

    Article  PubMed  CAS  Google Scholar 

  4. Ruiz de Almodovar C, Ruiz-Ruiz C, Munoz-Pinedo C et al (2001) The differential sensitivity of Bcl-2-overexpressing human breast tumor cells to TRAIL or doxorubicin-induced apoptosis is dependent on Bcl-2 protein levels. Oncogene 20:7128–7133

    Article  PubMed  CAS  Google Scholar 

  5. Gariboldi MB, Ravizza R, Riganti L et al (2003) Molecular determinants of intrinsic resistance to doxorubicin in human cancer cell lines. Int J Oncol 22:1057–1064

    PubMed  CAS  Google Scholar 

  6. Pommier Y, Sordet O, Antony S et al (2004) Apoptosis defects and chemotherapy resistance: molecular interaction maps and networks. Oncogene 23:2934–2949

    Article  PubMed  CAS  Google Scholar 

  7. Prost S (1995) Mechanisms of resistance to topoisomerases poisons. Gen Pharmacol 26:1673–1684

    Google Scholar 

  8. Vimalachandran D, Costello E (2004) Proteomic technologies and their application to pancreatic cancer. Expert Rev Proteomics 1:493–501

    Article  PubMed  CAS  Google Scholar 

  9. Chen R, Pan S, Brentnall TA, Aebersold R (2005) Proteomic profiling of pancreatic cancer for biomarker discovery. Mol Cell Proteomics 4:523–533

    Article  PubMed  CAS  Google Scholar 

  10. Yang YX, Sun XF, Cheng AL et al (2009) Increased expression of HSP27 linked to vincristine resistance in human gastric cancer cell line. J Cancer Res Clin Oncol 135:181–189

    Article  PubMed  CAS  Google Scholar 

  11. Shi YQ, Hu WH, Yin F et al (2004) Regulation of drug sensitivity of gastric cancer cells by human calcyclin-binding protein (CacyBP). Gastric Cancer 7:160–166

    Article  PubMed  CAS  Google Scholar 

  12. Chen R, Yi EC, Donohoe S et al (2005) Pancreatic cancer proteome: the proteins that underlie invasion, metastasis, and immunologic escape. Gastroenterology 129:1187–1197

    Article  PubMed  CAS  Google Scholar 

  13. Shekouh AR, Thompson CC, Prime W et al (2003) Application of laser capture microdissection combined with two-dimensional electrophoresis for the discovery of differentially regulated proteins in pancreatic ductal adenocarcinoma. Proteomics 3:1988–2001

    Article  PubMed  CAS  Google Scholar 

  14. Zhu F, Wang Y, Zeng S, Fu X, Wang L, Cao J (2009) Involvement of Annexin A1 in multidrug resistance of K562/ADR cells identified by the proteomic study. OMICS 13:467–476

    Article  PubMed  CAS  Google Scholar 

  15. Tong A, Zhang H, Li Z et al (2007) Proteomic analysis of liver cancer cells treated with suberonylanilide hydroxamic acid. Cancer Chemother Pharmacol 61:791–802

    Article  PubMed  Google Scholar 

  16. Hockel M, Vaupel P (2001) Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst 93:266–276

    Article  PubMed  CAS  Google Scholar 

  17. Brown JM (1999) The hypoxic cell: a target for selective cancer therapy—eighteenth Bruce F. Cain Memorial Award lecture. Cancer Res 59:5863–5870

    PubMed  CAS  Google Scholar 

  18. Evans SM, Koch CJ (2003) Prognostic significance of tumor oxygenation in humans. Cancer Lett 195:1–16

    Article  PubMed  CAS  Google Scholar 

  19. Bos R, Groep PVD, Greijer AE et al (2003) Levels of hypoxia-inducible factor-1alpha independently predict prognosis in patients with lymph node negative breast carcinoma. Cancer 97:1573–1581

    Article  PubMed  Google Scholar 

  20. Teicher BA (1994) Hypoxia and drug resistance. Cancer Metastasis Rev 13:139–168

    Article  PubMed  CAS  Google Scholar 

  21. Voorhees PM, Dees EC, O’Neil B, Orlowski RZ (2003) The proteasome as a target for cancer therapy. Clin Cancer Res 9:6316–6325

    PubMed  CAS  Google Scholar 

  22. Ruggeri B, Miknyoczki S, Dorsey B et al (2009) The development and pharmacology of proteasome inhibitors for the management and treatment of cancer. Adv Pharmacol 57:91–135

    Article  PubMed  CAS  Google Scholar 

  23. Milano A, Iaffaioli RV, Caponigro F (2007) The proteasome: a worthwhile target for the treatment of solid tumours? Eur J Cancer 43:1125–1133

    Article  PubMed  CAS  Google Scholar 

  24. Adams J (2004) The proteasome: a suitable antineoplastic target. Nat Rev Cancer 4:349–360

    Article  PubMed  CAS  Google Scholar 

  25. Maniatis T (1999) A ubiquitin ligase complex essential for the NF-kappaB, Wnt/Wingless, and Hedgehog signaling pathways. Genes Dev 13:505–510

    Article  PubMed  CAS  Google Scholar 

  26. Ma MH, Yang HH, Parker K et al (2003) The proteasome inhibitor PS-341 markedly enhances sensitivity of multiple myeloma tumor cells to chemotherapeutic agents. Clin Cancer Res 9:1136–1144

    PubMed  CAS  Google Scholar 

  27. Olofsson B (1999) Rho guanine dissociation inhibitors: pivotal molecules in cellular signalling. Cell Signal 11:545–554

    Article  PubMed  CAS  Google Scholar 

  28. Sasaki T, Takai Y (1998) The Rho small G protein family-Rho GDI system as a temporal and spatial determinant for cytoskeletal control. Biochem Biophys Res Commun 245:641–645

    Article  PubMed  CAS  Google Scholar 

  29. Golovanov AP, Chuang TH, DerMardirossian C et al (2001) Structure–activity relationships in flexible protein domains: regulation of rho GTPases by RhoGDI and D4 GDI. J Mol Biol 305:121–135

    Article  PubMed  CAS  Google Scholar 

  30. Fukumoto Y, Kaibuchi K, Hori Y et al (1990) Molecular cloning and characterization of a novel type of regulatory protein (GDI) for the rho proteins, ras p21-like small GTP-binding proteins. Oncogene 5:1321–1328

    PubMed  CAS  Google Scholar 

  31. Poland J, Schadendorf D, Lage H et al (2002) Study of therapy resistance in cancer cells with functional proteome analysis. Clin Chem Lab Med 40:221–234

    Article  PubMed  CAS  Google Scholar 

  32. Sinha P, Kohl S, Fischer J et al (2000) Identification of novel proteins associated with the development of chemoresistance in malignant melanoma using two-dimensional electrophoresis. Electrophoresis 21:3048–3057

    Article  PubMed  CAS  Google Scholar 

  33. Takano M, Goto T, Sakamoto M et al (2003) Identification of paclitaxel-resistance related genes by differential display using cDNA microarray in ovarian cancer cell lines. Proc Am Soc Clin Oncol 22:462

    Google Scholar 

  34. Zhang BL, Zhang YQ, Dagher MC et al (2005) Rho GDP dissociation inhibitor protects cancer cells against drug-induced apoptosis. Cancer Res 65:6054–6062

    Article  PubMed  CAS  Google Scholar 

  35. Zhang F, Zhang L, Zhang B et al (2009) Anxa2 plays a critical role in enhanced invasiveness of multidrug resistant human breast cancer cells. J Proteome Res 8:5041–5047

    Article  PubMed  CAS  Google Scholar 

  36. Kim A, Enomoto T, Serada S et al (2009) Enhanced expression of Annexin A4 in clear cell carcinoma of the ovary and its association with chemoresistance to carboplatin. Int J Cancer 125:2316–2322

    Article  PubMed  CAS  Google Scholar 

  37. Hütter G, Sinha P (2001) Proteomics for studying cancer cells and the development of chemoresistance. Proteomics 1:1233–1248

    Article  PubMed  Google Scholar 

  38. Sinha P, Poland J, Kohl S et al (2003) Study of the development of chemoresistance in melanoma cell lines using proteome analysis. Electrophoresis 24:2386–2404

    Article  PubMed  CAS  Google Scholar 

  39. Murphy L, Henry M, Meleady P, Clynes M, Keenan J (2008) Proteomic investigation of taxol and taxotere resistance and invasiveness in a squamous lung carcinoma cell line. Biochim Biophys Acta 1784:1184–1191

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by the grants from the National Natural Sciences Foundation of China (30801294), Fok Ying Tung Education Foundation (201080) and the special major science and technology project for “creation of major new drugs” of China (2009ZX09103-132).

Conflict of interest

The authors have no conflict of interest.

Author information

Authors and Affiliations

  1. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, People’s Republic of China

    Xingchen Peng, Fengming Gong, Gang Xie, Yuwei Zhao, Minghai Tang, Luoting Yu & Aiping Tong

  2. Department of Oncology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, China

    Xingchen Peng

Authors
  1. Xingchen Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fengming Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gang Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuwei Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Minghai Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Luoting Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Aiping Tong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aiping Tong.

Additional information

Xingchen Peng and Fengming Gong have contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Peng, X., Gong, F., Xie, G. et al. A proteomic investigation into adriamycin chemo-resistance of human leukemia K562 cells. Mol Cell Biochem 351, 233–241 (2011). https://doi.org/10.1007/s11010-011-0730-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-011-0730-8

Keywords

Search

Navigation