Comparative Label-free LC-MS/MS Analysis of Colorectal Adenocarcinoma and Metastatic Cells Treated with 5-Fluorouracil
| Autor: | Paul A. Lambert, Kerry M. Bauer, Amanda B. Hummon |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Antimetabolites
Antineoplastic RHOA Proteome Colorectal cancer Cell Adenocarcinoma Biochemistry Article Antioxidants Tandem Mass Spectrometry Cell Line Tumor medicine Cell Adhesion Humans Neoplasm Metastasis Cell adhesion Molecular Biology biology Reproducibility of Results medicine.disease Label-free quantification medicine.anatomical_structure Cell culture Cancer cell Immunology Cancer research biology.protein Fluorouracil Colorectal Neoplasms Chromatography Liquid |
| Popis: | A label-free mass spectrometric strategy was used to examine the effect of 5-fluorouracil (5-FU) on the primary and metastatic colon carcinoma cell lines, SW480 and SW620, with and without treatment. 5-FU is the most common chemotherapeutic treatment for colon cancer. Pooled biological replicates were analyzed by nanoLC-MS/MS and protein quantification was determined via spectral counting. Phenotypic and proteomic changes were evident and often similar in both cell lines. The SW620 cells were more resistant to 5-FU treatment, with an IC(50) 2.7-fold higher than that for SW480. In addition, both cell lines showed pronounced abundance changes in pathways relating to antioxidative stress response and cell adhesion remodeling due to 5-FU treatment. For example, the detoxification enzyme NQO1 was increased with treatment in both cell lines, while disparate members of the peroxiredoxin family, PRDX2 or PRDX5 and PRDX6, were elevated with 5-FU exposure in either SW480 or SW620, respectively. Cell adhesion-associated proteins CTNNB1 and RhoA showed decreased expression with 5-FU treatment in both cell lines. The differential quantitative response in the proteomes of these patient-matched cell lines to drug treatment underscores the subtle molecular differences separating primary and metastatic cancer cells. |
| Databáze: | OpenAIRE |
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