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

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/beta-catenin pathway, but induced an EGFR/IKK alpha/beta/NF-kappa B pathway with elevated cell cycle, metastasis and basal autophagy. C) 2014 Elsevier Ireland Ltd. All rights reserved.