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Identification of triosephosphate isomerase as an anti-drug resistance agent in human gastric cancer cells using functional proteomic analysis

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Abstract

Aims

Proteomic study was used to explore new multidrug resistance (MDR)-related proteins and clarify novel mechanism of MDR in gastric cancer.

Methods

Two-dimensional gel electrophoresis and the PDQuest software analysis were applied to compare the differential expression of MDR-related proteins in gastric cancer SGC7901 cells and drug-resistant SGC7901 cells (SGC7901/VCR) induced by vincristine sulfate (VCR). The differential protein dots were excised and further analyzed by matrix-assisted laser desorption ionization-time of flight mass spectrometry analysis (MALDI-TOF-MS).

Results

Nine differential expression proteins between the two cell lines were successfully identified by MALDI-TOF-MS. Triosephosphate isomerase (TPI), a glycolytic pathway enzyme, was identified as a downregulated protein in SGC7901/VCR cells. Further, Western blot analysis and semiquantitative RT-PCR confirmed its decreased expression in SGC7901/VCR cells. Sense vector pcDNA3.1-TPI was constructed and transfected into SGC7901/VCR. The sensitivity of TPI-SGC7901/VCR cells to adriamycin (ADR), VCR, 5-fluorouracil and cis-dichlorodiamine platinum, as well as the accumulation and retention to ADR, were significantly increased when compared to their control cell lines.

Conclusions

These results provide new MDR-related protein candidates, which are differentially expressed in the MDR cell line and its parental cell line including TPI, which may participate in the VCR-mediated MDR in human gastric cancer. Upregulation of TPI expression could partially reverse multidrug-resistant phenotype of SGC7901/VCR, which suggests that TPI may be an anti-drug resistance agent in gastric cancer and the candidate target to develop novel therapeutics for better treatment of gastric cancer.

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Abbreviations

MDR:

Multidrug resistance

GST:

Glutathione S-transferase

LRP:

Lung resistance protein

MRP:

Multidrug resistance-associated protein

PBS:

Phosphate-buffered saline

P-gp:

P-glycoprotein

RP:

Ribosomal protein

SDS:

Sodium dodecyl sulfate

MALDI-TOF-MS:

Matrix-assisted laser desorption ionization-time of flight-mass spectrometry

PMF:

Peptide mass fingerprint

TPI:

Triosephosphate isomerase

VCR:

Vincristine

ADR:

Adriamycin

5-Fu:

5-Fluorouracil

MMC:

Mitomycin C

CCDP:

cis-Dichlorodiamine platinum

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Acknowledgments

This work was supported by grants from National Natural Science Foundation of China (No. 30672399 and No. 30371762).

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Authors and Affiliations

  1. State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, 17 Changle Western Rd, 710032, Xi’an, Shaanxi Province, People’s Republic of China

    Xin Wang, Yuanyuan Lu, Yongquan Shi, Mei Lan, Zhenxiong Liu, Huihong Zhai & Daiming Fan

  2. Surgical Oncology Laboratory, Department of Surgery, Boston VA Medical Center, Boston University School of Medicine, Boston, MA, 02130, USA

    Jinghua Yang

Authors
  1. Xin Wang
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  2. Yuanyuan Lu
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  3. Jinghua Yang
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  4. Yongquan Shi
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  5. Mei Lan
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  6. Zhenxiong Liu
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  7. Huihong Zhai
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  8. Daiming Fan
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Corresponding author

Correspondence to Daiming Fan.

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Xin Wang and Yuanyuan Lu contributed equally to this work.

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Wang, X., Lu, Y., Yang, J. et al. Identification of triosephosphate isomerase as an anti-drug resistance agent in human gastric cancer cells using functional proteomic analysis. J Cancer Res Clin Oncol 134, 995–1003 (2008). https://doi.org/10.1007/s00432-008-0367-5

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  • DOI: https://doi.org/10.1007/s00432-008-0367-5

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