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

Ming-Cheng Chen; Nien-Hung Lee; Tsung-Jung Ho; Hsi-Hsien Hsu; Chia-Hua Kuo; Wei-Wen Kuo; Yueh-Min Lin; Fuu-Jen Tsai; Chang-Hai Tsai; Chih-Yang Huang

doi:10.1016/j.canlet.2014.03.023

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

Cancer Lett. 2014 Jul 10;349(1):51-60. doi: 10.1016/j.canlet.2014.03.023. Epub 2014 Apr 12.

Authors

Ming-Cheng Chen¹, Nien-Hung Lee², Tsung-Jung Ho³, Hsi-Hsien Hsu⁴, Chia-Hua Kuo⁵, Wei-Wen Kuo⁶, Yueh-Min Lin⁷, Fuu-Jen Tsai⁸, Chang-Hai Tsai⁹, Chih-Yang Huang¹⁰

Affiliations

¹ Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, ROC; Puli Branch, Taichung Veterans General Hospital, Nantou, Taiwan, ROC.
² Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, ROC.
³ Chinese Medicine Department, China Medical University Beigang Hospital, Yunlin, Taiwan, ROC.
⁴ Division of Colorectal Surgery, Mackay Memorial Hospital, Taipei, Taiwan, ROC; Mackay Junior College of Medicine, Nursing and Management College, Taipei, Taiwan, ROC.
⁵ Department of Sports Sciences, University of Taipei, Taipei, Taiwan, ROC.
⁶ Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, ROC.
⁷ 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.
⁸ Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan, ROC.
⁹ Department of Healthcare Administration, Asia University, Taichung, Taiwan, ROC.
¹⁰ 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.

PMID: 24726344
DOI: 10.1016/j.canlet.2014.03.023

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.

Keywords: Autophagy; CPT-11; Chemoresistance; Metastasis; NF-κB.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autophagy / drug effects*
Autophagy / physiology
Camptothecin / analogs & derivatives*
Camptothecin / pharmacology
Cell Cycle / drug effects
Cell Line, Tumor
Colonic Neoplasms / drug therapy*
Colonic Neoplasms / metabolism
Colonic Neoplasms / pathology*
ErbB Receptors / metabolism*
Humans
I-kappa B Kinase / metabolism
Irinotecan
NF-kappa B / metabolism*
Neoplasm Metastasis
Signal Transduction / drug effects
Topoisomerase I Inhibitors / pharmacology
Wnt Proteins / metabolism
beta Catenin / metabolism

Substances

CTNNB1 protein, human
NF-kappa B
Topoisomerase I Inhibitors
Wnt Proteins
beta Catenin
Irinotecan
EGFR protein, human
ErbB Receptors
I-kappa B Kinase
Camptothecin