دورية أكاديمية
أعرض في EDS

Relevance of the organic anion transporting polypeptide 1B3 (OATP1B3) in the personalized pharmacological treatment of hepatocellular carcinoma.

التفاصيل البيبلوغرافية
العنوان: Relevance of the organic anion transporting polypeptide 1B3 (OATP1B3) in the personalized pharmacological treatment of hepatocellular carcinoma.
المؤلفون: Asensio M; Experimental Hepatology and Drug Targeting (HEVEPHARM), University of Salamanca, Salamanca, Spain; Institute for Biomedical Research of Salamanca (IBSAL), Salamanca, Spain; Centro de Investigación Biomédica en Red de enfermedades Hepáticas y Digestivas (CIBEREHD), Carlos III National Institute of Health, Madrid, Spain., Herraez E; Experimental Hepatology and Drug Targeting (HEVEPHARM), University of Salamanca, Salamanca, Spain; Institute for Biomedical Research of Salamanca (IBSAL), Salamanca, Spain; Centro de Investigación Biomédica en Red de enfermedades Hepáticas y Digestivas (CIBEREHD), Carlos III National Institute of Health, Madrid, Spain., Macias RIR; Experimental Hepatology and Drug Targeting (HEVEPHARM), University of Salamanca, Salamanca, Spain; Institute for Biomedical Research of Salamanca (IBSAL), Salamanca, Spain; Centro de Investigación Biomédica en Red de enfermedades Hepáticas y Digestivas (CIBEREHD), Carlos III National Institute of Health, Madrid, Spain., Lozano E; Experimental Hepatology and Drug Targeting (HEVEPHARM), University of Salamanca, Salamanca, Spain; Institute for Biomedical Research of Salamanca (IBSAL), Salamanca, Spain; Centro de Investigación Biomédica en Red de enfermedades Hepáticas y Digestivas (CIBEREHD), Carlos III National Institute of Health, Madrid, Spain., Muñoz-Bellvís L; Institute for Biomedical Research of Salamanca (IBSAL), Salamanca, Spain; Service of General and Gastrointestinal Surgery, University Hospital of Salamanca, Salamanca, Spain; Centro de Investigación Biomédica en Red del Cáncer (CIBERONC), Carlos III National Institute of Health, Madrid, Spain., Sanchez-Vicente L; Experimental Hepatology and Drug Targeting (HEVEPHARM), University of Salamanca, Salamanca, Spain., Morente-Carrasco A; Experimental Hepatology and Drug Targeting (HEVEPHARM), University of Salamanca, Salamanca, Spain; Area of Physiology, Faculty of Health Sciences, University Rey Juan Carlos, Alcorcón, Madrid, Spain., Marin JJG; Experimental Hepatology and Drug Targeting (HEVEPHARM), University of Salamanca, Salamanca, Spain; Institute for Biomedical Research of Salamanca (IBSAL), Salamanca, Spain; Centro de Investigación Biomédica en Red de enfermedades Hepáticas y Digestivas (CIBEREHD), Carlos III National Institute of Health, Madrid, Spain. Electronic address: jjgmarin@usal.es., Briz O; Experimental Hepatology and Drug Targeting (HEVEPHARM), University of Salamanca, Salamanca, Spain; Institute for Biomedical Research of Salamanca (IBSAL), Salamanca, Spain; Centro de Investigación Biomédica en Red de enfermedades Hepáticas y Digestivas (CIBEREHD), Carlos III National Institute of Health, Madrid, Spain.
المصدر: Biochemical pharmacology [Biochem Pharmacol] 2023 Aug; Vol. 214, pp. 115681. Date of Electronic Publication: 2023 Jul 08.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Country of Publication: England NLM ID: 0101032 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2968 (Electronic) Linking ISSN: 00062952 NLM ISO Abbreviation: Biochem Pharmacol Subsets: MEDLINE
أسماء مطبوعة: Publication: Oxford : Elsevier Science
Original Publication: Oxford, New York [etc.] Paragamon Press.
مواضيع طبية MeSH: Antineoplastic Agents*/pharmacology , Antineoplastic Agents*/therapeutic use , Carcinoma, Hepatocellular*/drug therapy , Carcinoma, Hepatocellular*/metabolism , Liver Neoplasms*/drug therapy , Liver Neoplasms*/metabolism , Organic Anion Transporters*/metabolism, Animals ; Mice ; Cisplatin/metabolism ; Organic Anion Transporters, Sodium-Independent/metabolism ; Solute Carrier Organic Anion Transporter Family Member 1B3/genetics ; Humans
مستخلص: Although pharmacological treatment is the best option for most patients with advanced hepatocellular carcinoma (HCC), its success is very limited, partly due to reduced uptake and enhanced efflux of antitumor drugs. Here we have explored the usefulness of vectorizing drugs towards the organic anion transporting polypeptide 1B3 (OATP1B3) to enhance their efficacy against HCC cells. In silico studies (RNA-Seq data, 11 cohorts) and immunohistochemistry analyses revealed a marked interindividual variability, together with general downregulation but still expression of OATP1B3 in the plasma membrane of HCC cells. The measurement of mRNA variants in 20 HCC samples showed the almost absence of the cancer-type variant (Ct-OATP1B3) together with marked predominance of the liver-type variant (Lt-OATP1B3). In Lt-OATP1B3-expressing cells, the screening of 37 chemotherapeutical drugs and 17 tyrosine kinase receptors inhibitors (TKIs) revealed that 10 classical anticancer drugs and 12 TKIs were able to inhibit Lt-OATP1B3-mediated transport. Lt-OATP1B3-expressing cells were more sensitive than Mock parental cells (transduced with empty lentiviral vectors) to some Lt-OATP1B3 substrates (paclitaxel and the bile acid-cisplatin derivative Bamet-UD2), but not to cisplatin, which is not transported by Lt-OATP1B3. This enhanced response was abolished by competition with taurocholic acid, a known Lt-OATP1B3 substrate. Tumors subcutaneously generated in immunodeficient mice by Lt-OATP1B3-expressing HCC cells were more sensitive to Bamet-UD2 than those derived from Mock cells. In conclusion, Lt-OATP1B3 expression should be screened before deciding the use of anticancer drugs substrates of this carrier in the personalized treatment of HCC. Moreover, Lt-OATP1B3-mediated uptake must be considered when designing novel anti-HCC targeted drugs.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: Chemoresistance; Drug transport; Liver cancer; Targeted therapy; Tyrosine kinase inhibitors
المشرفين على المادة: 0 (Antineoplastic Agents)
0 (Bamet-UD2)
Q20Q21Q62J (Cisplatin)
0 (Organic Anion Transporters)
0 (Organic Anion Transporters, Sodium-Independent)
0 (Solute Carrier Organic Anion Transporter Family Member 1B3)
تواريخ الأحداث: Date Created: 20230710 Date Completed: 20230804 Latest Revision: 20230804
رمز التحديث: 20240628
DOI: 10.1016/j.bcp.2023.115681
PMID: 37429423
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-2968
DOI:10.1016/j.bcp.2023.115681