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. 2020 Jul;14(4):e1900080.
doi: 10.1002/prca.201900080. Epub 2020 Mar 12.

Proteomic Analysis Reveals that EPHX1 Contributes to 5-Fluorouracil Resistance in a Human Hepatocellular Carcinoma Cell Line

Rui Sun  1   2   3   4   5 , Chengyong Dong  1   2   3 , Rui Li  1   2   3 , Hongwei Chu  4   6 , Jianhui Liu  4 , Dingjun Hao  7 , Lihua Zhang  4 , Baofeng Zhao  4 , Liming Wang  1   2   3 , Yukui Zhang  4
Affiliations

Proteomic Analysis Reveals that EPHX1 Contributes to 5-Fluorouracil Resistance in a Human Hepatocellular Carcinoma Cell Line

Rui Sun et al. Proteomics Clin Appl. 2020 Jul.

Abstract

Purpose: The extensive drug resistance of hepatocellular carcinoma (HCC) has become a major cause of chemotherapy failure. A deeper understanding of the drug resistance mechanism of tumor cells is very significant for improving the clinical prognosis of patients with HCC.

Experimental design: In this study, proteomic studies on the composition of 5-fluorouracil (5-Fu) resistant Bel/5Fu cell line and its parent Bel7402 cell line by using an ionic liquid assisted proteins extraction method with the advantage of extracting plasma membrane proteins to a wider extent are performed. Then the expression level and function of differentially expressed plasma membrane proteins are verified.

Results: In total, 25 plasma membrane proteins are shown differentially expressed in Bel/5Fu compared with Bel7402. Western blot analysis results further confirmed that the EPHX1 PLIN2 RAB27B SLC4A2 are upregulated in Bel/5Fu cells in accordance with the proteomics data. Moreover, cell viability assay and clonogenic survival assay results demonstrated that EPHX1 is closely related to the chemoresistance of Bel/5Fu to 5-Fu.

Conclusions and clinical relevance: Plasma membrane protein EPHX1 is closely related to the chemotherapy resistance of Bel/5Fu cells and can be used as a new drug target to improve the clinical prognosis of patients with HCC.

Keywords: chemoresistance; hepatocellular carcinoma; ionic liquid; proteomics.

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