F127 poloxamer effect on cytotoxicity induction of tumour cell cultures treated with doxorubicin

GENTILE, EMILIANO ALBERTO; CASTRONUOVO, CYNTHIA CECILIA; CUESTAS, MARÍA LUJÁN; GÓMEZ, NATALIA; DAVIO, CARLOS; OUBIÑA, JOSÉ RAÚL; MATHET, VERÓNICA LIDIA

JOURNAL OF PHARMACY AND PHARMACOLOGY

PHARMACEUTICAL PRESS-ROYAL PHARMACEUTICAL SOC GREAT BRITIAN

Año: 2019 vol. 71 p. 1655 - 1662

0022-3573

Introduction Hepatocellular carcinoma is the most common liver malignancyand the third leading cause of cancer death worldwide. One crucial limitation inthe pharmacotherapy for this tumour is its chemotherapy-resistant nature producedby the overexpression of several members of the ATP-binding cassette proteinfamily that efflux drugs out of cells, as observed with the breast cancerresistant protein (BCRP).Objectives This study aimed to assess the ability of Pluronic F127 to reversethe multidrug resistance phenotype in two human hepatocellular cell lines.Methods PLC/PRF/5 and SKHep1 cells were exposed to Pluronic F127 at severalconcentrations. The effect of F127 on BCRP expression (mRNA and protein),mitochondrial transmembrane potential and cell hypodiploidy wasassessed. Finally, the effect of this copolymer on cytotoxicity of doxorubicin inboth hepatoma cell lines was investigated, as expressed by its reverse resistanceindex.Key findings It was demonstrated that F127 in both cell lines contributes tochemosensitization, as shown by BCRP down-regulation, an altered mitochondrialtransmembrane potential and hypodiploidy and reverse resistance index values.A remarkable dependence of these effects significantly correlated with thecopolymer concentration.Conclusions These findings further uncover the potential usefulness of thiscopolymer as multidrug resistance reversal agent, increasing the efficacy of cancertherapies