Downregulation of Foxc2 enhances apoptosis induced by 5-fluorouracil through activation of MAPK and AKT pathways in colorectal cancer

Oncology Letters
Chao YangWen-Ting Liao

Abstract

The chemotherapy drug 5-fluorouracil (5-FU) is fundamental for the treatment of colorectal cancer (CRC); however, drug resistance to 5-FU may occasionally occur. Abnormal expression of Forkhead box C2 gene (Foxc2) has been identified in several human cancers, but the role of Foxc2 in the progression of CRC remains unclear. The present study established a stable Foxc2-short hairpin (sh)RNA cell line, which was confirmed by western blot analysis and quantitative polymerase chain reaction. The Foxc2-shRNA cells were treated with 5-FU and the cell viability was determined by an MTT assay. Western blot analysis was performed to investigate the signaling pathway involved in 5-FU treatment. The present study identified that 5-FU increased the percentage of apoptotic CRC cells among the Foxc2/RNA interference-transfected cells compared with cells transfected with an empty vector. Therefore, the downregulation of Foxc2, induced by 5-FU, may enhance apoptosis by the downregulation of apoptotic factors, including B cell lymphoma-2 and pro-caspase-3, in Foxc2-shRNA CRC cells. Furthermore, the mitogen-activated protein kinase (MAPK) and phosphatidylinositide 3-kinases/protein kinase B (PI3K/AKT) pathways were essential for the sensitization...Continue Reading

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Citations

Nov 22, 2017·Scientific Reports·Tânia R MielckeMaria M Campos
Mar 30, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Ji YangYunmei Yang
Jul 24, 2020·International Journal of Molecular Sciences·Daniela TavianMatteo Bertelli

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