TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000285238
  • Gene Name:ABCC3
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:qPCR
  • mRNA Pathway:NA
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:DB00515 and DB00398
  • Drug Name:Cisplatin and Sorafenib
  • Drug Method:down-regulated the gene expression

Disease basic infommation

  • Disease:cholangiocarcinoma
  • Tissue:

Other information

  • Title:Sensitizing cholangiocarcinoma to chemotherapy by inhibition of the drug-export pump MRP3
  • Journal:Biomedicine & Pharmacotherapy
  • Published:2024
  • PubMed ID:39405909
  • Abstract:Aims:Drug export through ABC proteins hinders cancer response to chemotherapy. Here, we have evaluated the relevance of MRP3 (ABCC3) in cholangiocarcinoma (CCA) as a potential target to overcome drug resistance. Methods:Gene expression was analyzed in silico using the TCGA-CHOL database and experimentally (mRNA and protein) in resected CCA tumors. The effect of manipulating MRP3 function/expression was evaluated in vitro and in vivo. Results:High MRP3 expression at the plasma membrane of human CCA cells was found. MRP3 overexpression in HEK293T cells selectively impaired the cytotoxic effect of etoposide, cisplatin, SN-38, and mitoxantrone. Reduced MRP3 activity with shRNAs or pan-MRP blockers enhanced the sensitivity to these drugs. MRP3 interaction with natural and semisynthetic compounds (≈40,000) was evaluated by virtual drug screening and molecular docking. Two identified potential MRP3 inhibitors (EM-114, EM-188), and sorafenib impaired MRP3 transport activity and enhanced sensitivity of CCA cells to etoposide and cisplatin. The antitumor effect of cisplatin in the mouse xenograft model was enhanced by co-treatment with sorafenib, which was accompanied by a higher intratumor accumulation of cisplatin. Conclusions:Genetic and pharmacological MRP3 inhibition enhances the anti-CCA effect of several drugs, which constitutes a promising strategy to improve the response to chemotherapy in CCA patients.
@Copyright Harbin Medical University
　The 2nd Affiliated Hospital of Harbin Medical University
　 备案号：鲁ICP备2022025566号-3