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Current Cancer Drug Targets

Author(s): Lu Dong, Sifan Liu, Wenjing Sun, Siying Liu, Nan Zhang* and Shutian Zhang*

DOI: 10.2174/0115680096337375240801080008

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Mitochondrial Deoxyguanosine Kinase Induces 5-Fluorouracil Chemotherapy Sensitivity through Autophagy

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Abstract

Aims: The purpose of this study was to investigate the role of DGUOK in the progression of colorectal cancer (CRC) and its impact on the sensitivity of CRC cells to 5-FU treatment.

Methods: We conducted bioinformatics analysis and qRT-PCR to evaluate DGUOK expression in CRC tissues/cells. Cell viability of CRC cells treated with 5-FU was assessed using CCK-8 and colony formation assays. Autophagy levels were determined through immunofluorescence assays and Western blot analysis. Additionally, the influence of p-p38 on autophagy was investigated via Western blotting. A rescue assay was performed to confirm whether DGUOK/p38 affects 5-FU sensitivity in CRC cells through autophagy.

Results: Our findings indicate that DGUOK is upregulated in CRC tissues compared to normal tissues, correlating with increased cell proliferation and migration. Functionally, inhibition of DGUOK enhances autophagy, thereby decreasing the sensitivity of CRC cells to 5-FU. This effect is partly mediated by DGUOK's impact on the mitogen-activated protein kinase (MAPK) pathway, specifically promoting the phosphorylation of p38 MAPK, a crucial regulator in autophagy pathways.

Conclusion: These results suggest that DGUOK could serve as a novel marker for predicting the efficacy of 5-FU in CRC treatment.

Keywords: Colorectal cancer, deoxyguanosine kinase, autophagy, 5-fluorouracil, p38 MAPK, chemotherapy sensitivity.

Graphical Abstract

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