Suppression of ID1 expression in colon cancer cells increases sensitivity to 5-fluorouracil

• Authors: Tomasz Przybyła , Monika Sakowicz-Burkiewicz , Izabela Maciejewska , Hanna Bielarczyk , Tadeusz Pawełczyk
• Languages of publication: EN

Abstracts

EN

Adjuvant chemotherapy with 5-fluorouracil remains the basic treatment for patients with advanced colorectal carcinoma. The major obstacle in successful treatment is the ability of CRC cells to acquire chemoresistance. Here we examined the impact of ID1 silencing on the sensitivity of CRC cells to 5-FU. To suppress ID1 expression in HT-29 and HCT-116 cells the cells were transduced with a lentiviral vector carrying the ID1 silencing sequence. Cells with silenced ID1 showed altered expression of epithelial and mesenchymal markers and exhibited increased proliferation rate compared to the parental cells. HCT-116 cells with suppressed ID1 became sensitized to 5-FU and this was not observed in HT-29 cells. Silencing ID1 resulted in altered expression of genes encoding enzymes metabolizing 5-FU. HT-29 cells with suppressed ID1 had significantly reduced mRNA level for thymidine phosphorylase, uridine-cytydine kinase 2 and dihydropyrimidine dehydrogenase. ID1 suppression in HCT-116 cells resulted in an increase of mRNA level for thymidine phosphorylase, thymidine kinase and uridine-cytydine kinase 2 with concurrent drop of dihydropyrimidine dehydrogenase and thymidylate synthetase mRNA levels. In conclusion, ID1 expression impacts the sensitivity of colon cancer cells to 5-FU and may be considered as a potential predictive marker in CRC treatment.

Keywords

EN

colon cancer; ID1; 5-fluorouracil; TYMP; TK; UCK2; DYPD; TYMS.

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2017
• Volume: 64
• Issue: 2
• Pages: 315-322

Dates

published

2017

received

2016-09-07

revised

2017-02-06

accepted

2017-02-21

(unknown)

2017-05-17

Contributors

author

Tomasz Przybyła

• Department of Molecular Medicine, Medical University of Gdansk, Gdańsk, Poland

author

Monika Sakowicz-Burkiewicz

• Department of Molecular Medicine, Medical University of Gdansk, Gdańsk, Poland

author

Izabela Maciejewska

• Department of Molecular Medicine, Medical University of Gdansk, Gdańsk, Poland

author

Hanna Bielarczyk

• Departemnt of Laboratory Medicine, Medical University of Gdansk, Gdańsk, Poland

author

Tadeusz Pawełczyk

• Department of Molecular Medicine, Medical University of Gdansk, Gdańsk, Poland

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Identifiers

DOI

10.18388/abp.2016_1421