Document Detail


Autophagy: novel action of panitumumab in colon cancer.
MedLine Citation:
PMID:  20044619     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Panitumumab, a fully-human monoclonal antibody raised against epidermal growth factor receptor (EGFR), has been approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) for the treatment of patients with EGFR-expressing metastatic colorectal carcinoma (mCRC) after failure of standard chemotherapy. Additionally, the guideline of the EMEA includes the use of panitumumab in patients with wild-type KRAS. The goal of the current study was to evaluate the effect of panitumumab on colon cancer cells, proliferation, apoptosis, necrosis, cell cycle arrest and autophagy. The effect of panitumumab on the redox status of the cells was also studied. MATERIALS AND METHODS: The cell lines Caco-2, DLD-1 and HT-29 which differ in their expression of EGFR and HER-2 were used. Cell proliferation and apoptosis/necrosis were measured by methyl tetrazolium (MTT) assay and annexin V/propidium iodide assay, respectively. Cell cycle arrest was estimated by propidium iodide assay and autophagy was detected using Western blot analysis. Spectrophotometrical quantification of glutathione (GSH) levels and an analysis of KRAS sequence were applied. RESULTS: Panitumumab reduced proliferation only in the DLD-1 cells despite the mutated KRAS in this cell line. However, panitumumab did not affect DLD-1 cell apoptosis, necrosis or cell cycle progression. Interestingly, immunoblotting analysis revealed that panitumumab increased protein levels of beclin-1, a marker of autophagy. In addition, an increase in the GSH level was noted following panitumumab treatment reflecting an imbalance in the redox status of the cells. CONCLUSION: Panitumumab affects colon cancer cell proliferation independently of KRAS mutations and EGFR protein levels, possibly through the induction of autophagy.
Authors:
Efstathia Giannopoulou; Anna Antonacopoulou; Panagiota Matsouka; Haralabos P Kalofonos
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  29     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2010-01-01     Completed Date:  2010-03-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  5077-82     Citation Subset:  IM    
Affiliation:
Clinical Oncology Laboratory, Division of Oncology, Department of Medicine, University Hospital of Patras, Patras Medical School, Rio 26504, Greece.
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MeSH Terms
Descriptor/Qualifier:
Antibodies, Monoclonal / pharmacology*
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Autophagy
Cell Cycle / drug effects*
Cell Proliferation / drug effects*
Colonic Neoplasms / drug therapy*,  pathology*
DNA, Neoplasm / genetics
Glutathione / metabolism
Humans
Immunoblotting
Mutation
Oxidation-Reduction
Polymerase Chain Reaction
Proto-Oncogene Proteins / genetics
Tumor Cells, Cultured
ras Proteins / genetics
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antineoplastic Agents; 0/DNA, Neoplasm; 0/KRAS protein, human; 0/Proto-Oncogene Proteins; 0/panitumumab; 70-18-8/Glutathione; EC 3.6.5.2/ras Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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