ALDH1A3 upregulation and spontaneous metastasis formation is associated with acquired chemoresistance in colorectal cancer cells

BMC Cancer
E DurinikovaM Matuskova

Abstract

Efficiency of colorectal carcinoma treatment by chemotherapy is diminished as the resistance develops over time in patients. The same holds true for 5-fluorouracil, the drug used in first line chemotherapy of colorectal carcinoma. Chemoresistant derivative of HT-29 cells was prepared by long-term culturing in increasing concentration of 5-fluorouracil. Cells were characterized by viability assays, flow cytometry, gene expression arrays and kinetic imaging. Immunomagnetic separation was used for isolation of subpopulations positive for cancer stem cells-related surface markers. Aldehyde dehydrogenase expression was attenuated by siRNA. In vivo studies were performed on SCID/bg mice. The prepared chemoresistant cell line labeled as HT-29/EGFP/FUR is assigned with different morphology, decreased proliferation rate and 135-fold increased IC50 value for 5-fluorouracil in comparison to parental counterparts HT-29/EGFP. The capability of chemoresistant cells to form tumor xenografts, when injected subcutaneously into SCID/bg mice, was strongly compromised, however, they formed distant metastases in mouse lungs spontaneously. Derived cells preserved their resistance in vitro and in vivo even without the 5-fluorouracil selection pressur...Continue Reading

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Aug 25, 2019·Cancers·Silvia SchmidtovaLucia Kucerova
Jan 8, 2019·World Journal of Stem Cells·Mariel E Toledo-GuzmánElizabeth Ortiz-Sánchez
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Methods Mentioned

BETA
flow cytometry
PCR
Assay
FCS
transfection
xenografts
xenograft
flow

Software Mentioned

FCS Express
IncuCyte [UNK] 2016A
IncuCyte
GraphPad Prism®
FacsDiva
CFX

Related Concepts