title: Resistance to irinotecan (CPT-11) activates epidermal growth factor receptor/nuclear factor kappa B and increases cellular metastasis and autophagy in LoVo colon cancer cells.
abstract: Chemotherapy is usually applied to treat colon cancer but leads to chemoresistance, and increased metastasis and invasion. The main focus of this study is to observe effects of resistance to irinotecan (CPT-11) on metastasis, invasion and autophagy in CPT-11 resistant (CPT-11-R) LoVo colon cancer cells. CPT-11, a topoisomerase I inhibitor and a first-line chemotherapeutic drug, is used to treat colon cancer. CPT-11-R cells were constructed in a step-wise fashion with increasing CPT-11 doses. The CPT-11-R strain had a significantly lower expression of Wnt/β-catenin pathway, but induced an EGFR/IKKα/β/NF-κB pathway with elevated cell cycle, metastasis and basal autophagy.
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, ROC; Puli Branch, Taichung Veterans General Hospital, Nantou, Taiwan, ROC.
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Chen
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Nien-Hung
authors.initials: NH
authors.lastname: Lee
authors.affiliation: Chinese Medicine Department, China Medical University Beigang Hospital, Yunlin, Taiwan, ROC.
authors.forename: Tsung-Jung
authors.initials: TJ
authors.lastname: Ho
authors.affiliation: Division of Colorectal Surgery, Mackay Memorial Hospital, Taipei, Taiwan, ROC; Mackay Junior College of Medicine, Nursing and Management College, Taipei, Taiwan, ROC.
authors.forename: Hsi-Hsien
authors.initials: HH
authors.lastname: Hsu
authors.affiliation: Department of Sports Sciences, University of Taipei, Taipei, Taiwan, ROC.
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Kuo
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Kuo
authors.affiliation: Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan, ROC; Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan, ROC.
authors.forename: Yueh-Min
authors.initials: YM
authors.lastname: Lin
authors.affiliation: Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.affiliation: Department of Healthcare Administration, Asia University, Taichung, Taiwan, ROC.
authors.forename: Chang-Hai
authors.initials: CH
authors.lastname: Tsai
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, ROC; Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan, ROC; Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan, ROC. Electronic address: cyhuang@mail.cmu.edu.tw.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
mesh_terms: D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D000077146:Irinotecan; D016328:NF-kappa B / Q000378:metabolism*; D009362:Neoplasm Metastasis; D015398:Signal Transduction / Q000187:drug effects; D059004:Topoisomerase I Inhibitors / Q000494:pharmacology; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; D016328:NF-kappa B; D059004:Topoisomerase I Inhibitors; D051153:Wnt Proteins; D051176:beta Catenin; D000077146:Irinotecan; C512478:EGFR protein, human; D066246:ErbB Receptors; D051550:I-kappa B Kinase; D002166:Camptothecin
keywords: Autophagy; CPT-11; Chemoresistance; Metastasis; NF-κB