Doublecotin-Like Kinase 1 Increases Chemoresistance of Colorectal Cancer Cells through the Anti-Apoptosis Pathway

Journal of Stem Cell Research & Therapy
Lianna LiHao Mei

Abstract

Colorectal Cancer (CRC) is the third most common cancer diagnosed and the second leading cause of cancer-related deaths in the United States. Cancer Stem Cells (CSCs) are believed to be the primary reason for the recurrence of CRC. Specific stem cell marker, doublecortin-like kinase 1 (DCLK1) plays critical roles in the tumorigenesis and progression of CRC. Up-regulation of DCLK1 is correlated with poor prognosis. Whether DCLK1 is correlated with enhanced chemoresistance of CRC cells is unclear. We aim to reveal the association of DCLK1 with chemoresistance of CRC cells and the underlying molecular mechanisms. Stable DCLK1 over-expression cells (DCLK1+) were established using the HCT116 cells (WT). DCLK1+ and WT cells were treated with 5-Fluorouracil (5-Fu) at different doses for 24 or 48 hours. MTT assay was used to evaluate cell viability and IC50 of 5-Fu was determined. Quantitative real-time PCR was applied to determine the gene expression of caspase-3 (casp-3), casp-4, and casp-10. Cleaved casp-3 expression was investigated using Western blot and immunofluorescence. Our results demonstrated that IC50 of 5-Fu for the DCLK1+ cells was significantly higher than that of the WT cells for both 24 and 48-hour treatment (p=0.002 a...Continue Reading

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