title: Adenomatous polyposis coli determines sensitivity to the EGFR tyrosine kinase inhibitor gefitinib in colorectal cancer cells.
abstract: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been used to treat colorectal cancer (CRC). However, resistance to EGFR-TKIs presents a great challenge for the treatment of CRC, and the mechanisms of resistance are poorly understood. The adenomatous polyposis coli (APC) protein has been known to contribute to the carcinogenesis of CRC. However, its role in the sensitivity of CRC cells to gefitinib has not been investigated. Human CRC HCT-116 (wild-type APC) and HT-29 (mutant APC) cells were used to investigate the effect of APC on the sensitivity of CRC cells to gefitinib. The MTT assay was used to measure cell viability after exposure to gefitinib. Cell apoptosis, migration and invasion were determined by flow cytometry, wound healing assay and transwell assay, respectively. Knockdown and overexpression of APC were performed, and activation of the EGFR and its downstream pathway was determined. Gefinitib inhibited viability, promoted apoptosis, and reduced the migration of HCT-116 and HT-29 cells. HT-29 cells exhibited increased sensitivity to gefinitib when compared to HCT-116 cells. Knockdown of APC expression increased the sensitivity of HCT-16 cells to gefitinib, accompanied by downregulation of pEGFR, p-AKT and pERK1/2. In contrast, overexpression of APC decreased the sensitivity of HT-29 cells to gefitinib, accompanied by upregulation of pEGFR, p-AKT and pERK1/2. APC plays an important role in the sensitivity of CRC cells to gefitinib. APC may represent a potential therapeutic target for the treatment of CRC.
authors.affiliation: Department of Gastrointestinal Endoscopy, The First Hospital of China Medical University, Heping, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Yining
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Science, China Medical University, Heping, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Qinghuan
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: Department of Gastrointestinal Endoscopy, The First Hospital of China Medical University, Heping, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Huijing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Endoscopy, The First Hospital of China Medical University, Heping, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Xuren
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Gastrointestinal Endoscopy, The First Hospital of China Medical University, Heping, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Ge
authors.affiliation: Department of Gastrointestinal Endoscopy, The First Hospital of China Medical University, Heping, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Gastrointestinal Endoscopy, The First Hospital of China Medical University, Heping, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Guan
authors.affiliation: Department of Gastrointestinal Endoscopy, The First Hospital of China Medical University, Heping, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Mingjun
authors.initials: M
authors.lastname: Sun
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005434:Flow Cytometry; D000077156:Gefitinib; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib