Autophagy: Novel Action of Panitumumab in Colon Cancer

作者: Anna Antonacopoulou , Efstathia Giannopoulou , Haralabos P. Kalofonos , Panagiota Matsouka

DOI:

关键词:

摘要: 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) European Medicines Agency (EMEA) for treatment of patients with EGFR- expressing metastatic colorectal carcinoma (mCRC) after failure standard chemotherapy. Additionally, guideline EMEA includes use panitumumab in wild-type KRAS. The goal current study was to evaluate effect on colon cancer cells, proliferation, apoptosis, necrosis, cell cycle arrest autophagy. redox status cells also studied. Materials Methods: lines Caco-2, DLD-1 HT-29 which differ their expression EGFR HER-2 were used. Cell proliferation apoptosis/necrosis measured methyl tetrazolium (MTT) assay annexin V/propidium iodide assay, respectively. estimated propidium autophagy detected using Western blot analysis. Spectrophotometrical quantification glutathione (GSH) levels an analysis KRAS sequence applied. Results: Panitumumab reduced only despite mutated this line. However, did not affect necrosis or progression. Interestingly, immunoblotting revealed that increased protein beclin-1, marker In addition, increase GSH level noted following reflecting imbalance cells. Conclusion: affects independently mutations levels, possibly through induction Among most recent advances management (CRC) are immunotherapies targeting

参考文章(44)
Sigal Blau, Abraham Rubinstein, Paul Bass, Chandar Singaram, Ron Kohen, Differences in the reducing power along the rat GI tract: lower antioxidant capacity of the colon. Molecular and Cellular Biochemistry. ,vol. 194, pp. 185- 191 ,(1999) , 10.1023/A:1006994800272
Anastasia Parthymou, Panagiotis Katsoris, Efstathia Giannopoulou, Evangelia Papadimitriou, Dimitris Kardamakis, Amifostine protects blood vessels from the effects of ionizing radiation. Anticancer Research. ,vol. 22, pp. 2821- 2826 ,(2002)
Todd Alekshun, Chris Garrett, Targeted therapies in the treatment of colorectal cancers. Cancer Control. ,vol. 12, pp. 105- 110 ,(2005) , 10.1177/107327480501200205
Xiao Huan Liang, Saadiya Jackson, Matthew Seaman, Kristy Brown, Bettina Kempkes, Hanina Hibshoosh, Beth Levine, None, Induction of autophagy and inhibition of tumorigenesis by beclin 1 Nature. ,vol. 402, pp. 672- 676 ,(1999) , 10.1038/45257
Tova Rainis, Irit Maor, Amos Lanir, Sergay Shnizer, Alexandra Lavy, Enhanced oxidative stress and leucocyte activation in neoplastic tissues of the colon. Digestive Diseases and Sciences. ,vol. 52, pp. 526- 530 ,(2007) , 10.1007/S10620-006-9177-2
Efstathia Giannopoulou, Anna Antonacopoulou, Konstantina Floratou, Athanasios G. Papavassiliou, Haralabos P. Kalofonos, Dual targeting of EGFR and HER-2 in colon cancer cell lines. Cancer Chemotherapy and Pharmacology. ,vol. 63, pp. 973- 981 ,(2009) , 10.1007/S00280-008-0820-9
Wu Zhang, Michael Gordon, Heinz‐Josef Lenz, Novel approaches to treatment of advanced colorectal cancer with anti-EGFR monoclonal antibodies. Annals of Medicine. ,vol. 38, pp. 545- 551 ,(2006) , 10.1080/09546630601070812
Yang Cao, Daniel J Klionsky, Physiological functions of Atg6/Beclin 1: a unique autophagy-related protein Cell Research. ,vol. 17, pp. 839- 849 ,(2007) , 10.1038/CR.2007.78