Proteomic investigation of 5‐fluorouracil resistance in a human hepatocellular carcinoma cell line

Abstract

Multi-drug resistance (MDR) is a major obstacle towards a successful treatment of hepatocellular carcinoma (HCC). The mechanisms of MDR are intricate and have not been fully understood. Therefore, we employed a cell-line model consisting of the 5-fluorouracil (5-FU) resistant BEL7402/5-FU cell line and its parental BEL7402 cell line. Using relative and absolute quantification (iTRAQ)-coupled 2D LC-MS/MS, a successfully exploited high-throughput proteomic technology, in total, 660 unique proteins were identified and 52 proteins showed to be differentially expressed in BEL7402/5-FU compared with BEL7402. Several differentially expressed proteins were further validated by Western blot and real-time quantitative RT-PCR analysis. Furthermore, the association of MDR with ANXA3, one of the highly expressed proteins in BEL7402/5-FU, was verified. Our study represents the first successful application of iTRAQ technology for MDR mechanisms analysis in HCC. Many of the differentially expressed proteins identified had not been linked to MDR in HCC before, which provide valuable information for further understanding of MDR.

Annexin A3 as a Prognostic Biomarker for Breast Cancer: A Retrospective Study

“…The highest expression of ANXA3 was detected in triple-negative breast cancer with poor prognosis as confirmed by the subsequent follow-up studies. Similar upregulation of the expression of ANXA3 is reported in prostate, ovarian, liver, rectal, and gastric cancers [10, 12, 24–27]. A positive correlation between the expression of annexin and breast cancer was established.…”

Characterization and Resistance Mechanisms of A 5-fluorouracil-resistant Hepatocellular Carcinoma Cell Line

“…It is easy to notice that the RIs of BEL-7402/5-FU to cytotoxic drugs in our study (Table 1) are much smaller than that reported by other studies where their RIs of BEL-7402/5-FU cells ranged 160-339.7 folds for 5-FU and 13.4-26.90 folds for ADM (Jin et al, 2002;Li et al, 2004;Tong et al, 2012). The wide variation between RIs of BEL-7402/5-FU established by different research teams might be mainly due to the difference in induction methods.…”

FUT family mediates the multidrug resistance of human hepatocellular carcinoma via the PI3K/Akt signaling pathway

“…1 The mechanisms underlying the MDR of cancer cells are complex, 2, 3 including increase in drug efflux, reduction in drug absorption, changes in the targets of anticancer drugs, decrease in drug activity, enhancement of DNA repair following damage, changes in signaling pathway and so on. Classic MDR is the consequence of overexpression of transporter proteins belonging to the ATP-binding cassette (ABC) family such as P-glycoprotein (P-gp) and MDR-related protein (MRP).…”