Mebendazole, an antiparasitic drug, inhibits drug transporters expression in preclinical model of gastric peritoneal carcinomatosis

Laine Celestino Pinto; Caroline de Fátima Aquino Moreira-Nunes; Bruno Moreira Soares; Rommel Mário Rodriguez Burbano; José Alexandre Rodrigues de Lemos; Raquel Carvalho Montenegro

doi:10.1016/j.tiv.2017.06.007

Mebendazole, an antiparasitic drug, inhibits drug transporters expression in preclinical model of gastric peritoneal carcinomatosis

Toxicol In Vitro. 2017 Sep:43:87-91. doi: 10.1016/j.tiv.2017.06.007. Epub 2017 Jun 9.

Authors

Laine Celestino Pinto¹, Caroline de Fátima Aquino Moreira-Nunes², Bruno Moreira Soares¹, Rommel Mário Rodriguez Burbano¹, José Alexandre Rodrigues de Lemos³, Raquel Carvalho Montenegro⁴

Affiliations

¹ Biological Science Institute, Federal University of Para, Belem, Pará, Brazil.
² Laboratory of Pharmacogenomics, Nucleus of Research and Development of Medicines (NPDM), Federal University of Ceara, Fortaleza, Ceará, Brazil.
³ Biological Science Institute, Federal University of Para, Belem, Pará, Brazil; Foundation Center for Hemotherapy and Hematology of Pará (HEMOPA), Laboratory of Genetics and Molecular Biology, Belem, Pará, Brazil.
⁴ Biological Science Institute, Federal University of Para, Belem, Pará, Brazil; Laboratory of Pharmacogenomics, Nucleus of Research and Development of Medicines (NPDM), Federal University of Ceara, Fortaleza, Ceará, Brazil. Electronic address: rc_montenegro@pq.cnpq.br.

PMID: 28606429
DOI: 10.1016/j.tiv.2017.06.007

Abstract

The present study aimed to investigate whether MBZ down-regulates drug transporter expression (ABCB1, ABCC1, SLC47A1). mRNA expression level of ABCB1, ABCC1 and SLC47A1 was evaluated by qPCR and protein expression levels MDR-1 was performed by western blotting in malignant ascites cells (AGP-01) treated with MBZ for 24h. The mRNA expression level of ABCB1 and ABCC1 significantly decreased at a 1.0μM of MBZ compared to negative control, while SLC47A1 extremely decreased at all tested concentrations of MBZ. Protein expression levels MDR-1 significantly decreased at a 1.0μM of MBZ compared to negative control. Therefore, our results showed MBZ may play an important role in inhibiting MDR gene expression in malignant ascites cells.

Keywords: Drug transporter; Gastric cancer cells; Inhibition; Mebendazole.

MeSH terms

Antiparasitic Agents / pharmacology*
Cell Line, Tumor
Drug Evaluation, Preclinical
Humans
Mebendazole / pharmacology*
Membrane Transport Proteins / genetics
Membrane Transport Proteins / metabolism*
Peritoneal Neoplasms / metabolism*
RNA, Messenger / metabolism
Stomach Neoplasms / metabolism*

Substances

Antiparasitic Agents
Membrane Transport Proteins
RNA, Messenger
Mebendazole