E Towu1, R Al-Mufti, M Winslet. 1. Department of Paediatric Surgery, Hospital for Sick Children, Great Ormond Street, London, England, UK.
Abstract
PURPOSE: The aim of this study was to quantify the uptake of anthracyclic cytotoxic drugs by hepatocellular carcinoma cells and the effect of Lipiodol, an iodinated poppy seed oil, on the uptake of anthracyclic cytotoxic conjugates by hepatocellular carcinoma (HCC) cells. METHODS: Monolayers of hepatocellular carcinoma cell line (HepG2) and a normal human hepatocyte cell line were exposed to 10 microg/mL doxorubicin or epirubicin with or without 2% lipiodol for 1 to 72 hours. The fluorescence intensity in the cytospin and fixed cell were measured using confocal laser scanning microscope. RESULTS: The uptake of both doxorubicin and epirubicin by the HCC cells was mainly cytoplasmic. The mean fluorescence intensity at 24 hours of lipiodol-doxorubicin-treated cells was increased to 80.7 pixel units, whereas doxorubicin-treated cells intensity was 47.9 pixel units (P <.05). Lipiodol did not have any effect on the uptake of epirubicin. Clonogenic assay confirmed a significant sensitivity difference between doxorubicin and epirubicin-treated hepatocellular carcinoma cell lines. CONCLUSIONS: Lipiodol has a selective effect on the uptake of certain cytotoxic agents. Lipiodol-doxorubicin-targeted treatment of hepatocellular carcinoma may improve the intracellular uptake and hence cytotoxicity of doxorubicin in vivo.
PURPOSE: The aim of this study was to quantify the uptake of anthracyclic cytotoxic drugs by hepatocellular carcinoma cells and the effect of Lipiodol, an iodinated poppy seed oil, on the uptake of anthracyclic cytotoxic conjugates by hepatocellular carcinoma (HCC) cells. METHODS: Monolayers of hepatocellular carcinoma cell line (HepG2) and a normal human hepatocyte cell line were exposed to 10 microg/mL doxorubicin or epirubicin with or without 2% lipiodol for 1 to 72 hours. The fluorescence intensity in the cytospin and fixed cell were measured using confocal laser scanning microscope. RESULTS: The uptake of both doxorubicin and epirubicin by the HCC cells was mainly cytoplasmic. The mean fluorescence intensity at 24 hours of lipiodol-doxorubicin-treated cells was increased to 80.7 pixel units, whereas doxorubicin-treated cells intensity was 47.9 pixel units (P <.05). Lipiodol did not have any effect on the uptake of epirubicin. Clonogenic assay confirmed a significant sensitivity difference between doxorubicin and epirubicin-treated hepatocellular carcinoma cell lines. CONCLUSIONS:Lipiodol has a selective effect on the uptake of certain cytotoxic agents. Lipiodol-doxorubicin-targeted treatment of hepatocellular carcinoma may improve the intracellular uptake and hence cytotoxicity of doxorubicin in vivo.
Authors: Marites P Melancon; Steven Yevich; Rony Avritscher; Adam Swigost; Linfeng Lu; Li Tian; Jossana A Damasco; Katherine Dixon; Andrea C Cortes; Nina M Munoz; Dong Liang; David Liu; Alda L Tam Journal: Drug Deliv Date: 2021-12 Impact factor: 6.419