Screening of anticancer drugs for chemoembolization of hepatocellular carcinoma.

  • Boulin M
  • Guiu S
  • Chauffert B
 et al. 
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Abstract

The aim of this study was to select the best candidate drug for transarterial chemoembolization by in-vitro cytotoxic evaluations of 11 anticancer drugs on three human hepatocellular carcinoma (HCC) cell lines. The SNU-398, HepG2, and SNU-449 human HCC cell lines were exposed for 30 min to 11 concentrations of doxorubicin, epirubicin, idarubicin, mitoxantrone, carboplatin, cisplatin, oxaliplatin, 5-fluorouracil, gemcitabine, mitomycin C, or paclitaxel. Cytotoxicity was measured using a quantitative colorimetric assay. For each drug and cell line, we calculated the drug concentration that caused 90% cell death (IC90). To enable comparisons of drugs with different concentration ranges, we computed the cytotoxic index (CyI) as the ratio of maximal drug concentration of more than IC90. Parameters were estimated using nonlinear regression models. Idarubicin was the most active drug on all three cell lines. With SNU-398 cells, the idarubicin CyI was 2.4-fold, 2.5-fold, 57-fold, 148-fold, and more than 58 748-fold higher than the CyIs of mitoxantrone, epirubicin, doxorubicin, gemcitabine, and other drugs, respectively. With HepG2 cells, the idarubicin CyI was 27-fold, 28-fold, 51-fold, and more than 1343-fold higher than the CyIs of doxorubicin, epirubicin, mitoxantrone, and other drugs, respectively. On the resistant SNU-449 cell line, the idarubicin CyI was 2.9-fold and 14-fold higher than the CyIs of paclitaxel and gemcitabine, respectively, the only other drugs effective on this cell line. Among 11 chemotherapeutic agents including doxorubicin, cisplatin, and epirubicin, the most effective on three HCC cell lines was idarubicin. Further clinical investigations are needed to evaluate the safety and efficacy of idarubicin for transarterial chemoembolization in HCC.

Author-supplied keywords

  • Antineoplastic Agents
  • Carcinoma, Hepatocellular
  • Cell Line, Tumor
  • Chemoembolization, Therapeutic
  • Colorimetry
  • Dose-Response Relationship, Drug
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms
  • Nonlinear Dynamics
  • Regression Analysis
  • administration & dosage
  • methods
  • pathology
  • therapy

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Authors

  • Mathieu Boulin

  • Severine Guiu

  • Bruno Chauffert

  • Serge Aho

  • Jean-Pierre Cercueil

  • Francois Ghiringhelli

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