4.5 Article

HnRNPK and PDI marked response to chemotherapy to human colorectal cancer cells

Journal

ELECTROPHORESIS
Volume 31, Issue 10, Pages 1731-1738

Publisher

WILEY
DOI: 10.1002/elps.200900495

Keywords

Biomarker; Chemotherapy; Colorectal cancer; Metastasis; Proteomics

Funding

  1. Shanghai Science and Technology Development [05DJ14010, 08140903000]
  2. Major Basic Research Program of Shanghai [07DZ19505]
  3. Ministry of Science and Technology of the People's Republic of China [2008CB517403]

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5-Fluorouracil has been the chemotherapy agent of first-choice for colorectal cancer for many years, but since there are no proven predictors of a patient's response to therapy, all patients receive similar treatment. Consequently, identification of biomarkers for therapeutic effect is crucial for the development of novel therapeutic strategies. Two human colorectal cancer cell lines of different metastatic potential (LoVo and SW480) were studied. IC50 of 5-FU for both cell lines were measured by 3-(4,5-dimethy-lthiazol-2-y1)2,5-diphenyltetrazolium assay and validated by cell cycle analysis. Then the cell lines were treated with 5-FU at 1050 concentration and protein was extracted for 2-DE. Differential protein spots were examined by MALDI-TOF/TOF MS. The expression levels of the different proteins were further confirmed by Western blot and immunofluorescence analyses. Eleven proteins were identified. Expression of heterogeneous nuclear ribonucleoprotein K (hnRNP K) in LoVo cells was higher than in SW480 cells, while protein disulfide isomerase (PDI) displayed the opposite trend. After treatment with 5-FU, the expression of hnRNP K in LoVo decreased more significantly than in SW480, while PD! in SW480 increased more significantly than in LoVo cells. Conclusion: hnRNP K and PDI in the two cell lines have different expression characteristics. The sensitivity to 5-FU is not consistent in tumor progression. It may assist in development of novel treatment strategies for colorectal cancer metastasis.

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