Dataset Information

5-fluorouracil (5-Fu) resistant Bel/5Fu cell line and its parent Bel7402 cell line

ABSTRACT: The extensive drug resistance of hepatocellular carcinoma (HCC) has become the main cause of chemotherapy failure. The mechanisms leading to drug resistance in tumor cells are not well understood. Previous studies demonstrated that plasma membrane proteins play important roles in mediating drug disposal or pharmacokinetics. Therefore, we performed 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 greater extent. In total, 4,532 unique proteins were quantified and 103 proteins (>2-fold change, p-value <0.05) including 25 plasma membrane proteins showed to be differentially expressed in Bel/5Fu compared with Bel7402. Western blot analysis results were further confirmed that the plasma membrane proteins EPHX1 PLIN2 RAB27B SLC4A2 were up-regulated in Bel/5Fu cells in accordance with the proteomics data. Moreover, cell viability assay and clonogenic survival assay results demonstrated that EPHX1 are closely related to the chemoresistance of Bel/5Fu to 5Fu.

ORGANISM(S): Homo Sapiens

SUBMITTER: Wang Liming

PROVIDER: PXD015917 | iProX | Sat Oct 19 00:00:00 BST 2019

REPOSITORIES: iProX

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Publications

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

Sun Rui R Dong Chengyong C Li Rui R Chu Hongwei H Liu Jianhui J Hao Dingjun D Zhang Lihua L Zhao Baofeng B Wang Liming L Zhang Yukui Y

Proteomics. Clinical applications 20200312 4

<h4>Purpose</h4>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.<h4>Experimental design</h4>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 m ...[more]

PMID: 32067389

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Project description:Background: Current protocols for the treatment of ovarian cancer include combination chemotherapy with a platinating agent and a taxane. However, many patients experience relapse of their cancer and the development of drug resistance is not uncommon, making successful second line therapy difficult to achieve. The objective of this study was to develop a cell line resistant to both carboplatin and docetaxel (dual drug resistant ovarian cell line A2780CBNDXL), along with single agent resistant lines (docetaxel resistant A2780DXL and carboplatin resistant A2780CBN), to investigate the mechanisms which underlie the development of dual drug resistance. Methods: The A2780 epithelial ovarian cancer cell line was used to select for isogenic carboplatin, docetaxel and dual drug resistant cell lines. A selection method of gradually increasing drug doses was implemented to avoid clonal selection. Resistance was confirmed using a clonogenic assay. Changes in gene expression associated with the development of drug resistance were determined by microarray analysis compared to parental co-culture control A2780CC. Changes in selected genes were validated by QPCR and immunoblotting. Results: Three isogenic cell lines were developed and resistance to each drug or the combination of drugs was confirmed. Development of resistance was accompanied by a reduced growth rate. The microarray and QPCR analyses showed that unique changes in gene expression occurred in the dual drug resistant cell line and that genes known to be involved in resistance could be identified in all cell lines. Conclusions: Novel changes in gene expression can occur in the development of dual drug resistance, indicating that dual drug resistance is not a simple combination of the changes occurring in single agent resistance Carboplatin, docetaxel (GSE26129) and carboplatin/docetaxel dual resistant cell lines of ovarian A2780 were generated for gene expression profilling. Two colour microarray of Agilent whole human genome nucleotide arrays was conducted with two replicate of both forward and reverse labellings for each cell line. Four arrays were used for this experiments. And it was four replicate of both forward and reverse labellings for A2780 cells. Eight arrays were used for this experiments

Dataset Information

5-fluorouracil (5-Fu) resistant Bel/5Fu cell line and its parent Bel7402 cell line

Publications

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

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