Adenomatous polyposis coli determines sensitivity to the EGFR tyrosine kinase inhibitor gefitinib in colorectal cancer cells
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.
Document Type: Research Article
Affiliations: 1: Department of Gastrointestinal Endoscopy, The First Hospital of China Medical University, Heping, Shenyang, Liaoning 110001, P.R. China 2: Department of Pharmacology, School of Pharmaceutical Science, China Medical University, Heping, Shenyang, Liaoning 110001, P.R. China
Publication date: 01 January 2014
- Oncology Reports is a monthly, peer-reviewed journal devoted to the publication of high quality original studies and reviews concerning a broad and comprehensive view of fundamental and applied research in oncology, focusing on carcinogenesis, metastasis and epidemiology.
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