Gemcitabine and Oxaliplatin, but Not Sorafenib or Paclitaxel, Have a Synergistic Effect with Yttrium-90 in Reducing Hepatocellular Carcinoma and Cholangiocarcinoma Cell Line Viability

J Vasc Interv Radiol. 2015 Dec;26(12):1874-78.e2. doi: 10.1016/j.jvir.2015.06.032.

Abstract

Synergy between yttrium-90 (90Y) and antineoplastic drugs was investigated. Viability of HepaRG (hepatocellular carcinoma) and HuCCT1 (cholangiocarcinoma) cells was studied through a tetrazolium dye reduction assay. A combination index (CI) was calculated, with CI < 1 denoting synergy and CI > 1 denoting antagonism. In HepaRG cells, gemcitabine showed synergy with 90Y (CI = 0.70 [95% confidence interval = 0.65-0.75]), whereas oxaliplatin (CI = 1.15 [1.08-1.21]), paclitaxel (CI = 1.26 [1.15-1.37]), and sorafenib (CI = 1.77 [1.65-1.89]) showed antagonism. In HuCCT1 cells, gemcitabine (CI = 0.54 [0.50-0.58]) and oxaliplatin (CI = 0.86 [0.82-0.90]) showed synergy with 90Y, whereas paclitaxel (CI = 1.18 [1.09-1.27]) and sorafenib (CI = 1.21 [1.12-1.30]) showed antagonism. These results suggest that gemcitabine and oxaliplatin should be tested in combination with 90Y radioembolization for treatment of liver cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Chemoradiotherapy / methods
  • Cholangiocarcinoma / pathology
  • Cholangiocarcinoma / therapy*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Drug Synergism
  • Humans
  • Niacinamide / administration & dosage
  • Niacinamide / analogs & derivatives*
  • Organoplatinum Compounds / administration & dosage*
  • Paclitaxel / administration & dosage*
  • Phenylurea Compounds / administration & dosage*
  • Pyridines / administration & dosage*
  • Radiation Tolerance / drug effects
  • Radiopharmaceuticals / administration & dosage
  • Sorafenib
  • Yttrium Radioisotopes / therapeutic use*

Substances

  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Phenylurea Compounds
  • Pyridines
  • Radiopharmaceuticals
  • Yttrium Radioisotopes
  • oxiplatin
  • Deoxycytidine
  • Niacinamide
  • Sorafenib
  • gemcitabine
  • Paclitaxel