title: Gemcitabine and Oxaliplatin, but Not Sorafenib or Paclitaxel, Have a Synergistic Effect with Yttrium-90 in Reducing Hepatocellular Carcinoma and Cholangiocarcinoma Cell Line Viability.
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.
authors.affiliation: Department of Medical Oncology, Centre Eugène Marquis, Av de la bataille Flandres Dunkerque, Rennes 35043, France; Inserm UMR991, Rennes, France. Electronic address: j.edeline@rennes.unicancer.fr.
authors.forename: Julien
authors.initials: J
authors.lastname: Edeline
authors.affiliation: Inserm UMR991, Rennes, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Coulouarn
authors.affiliation: Department of Medical Oncology, Centre Eugène Marquis, Av de la bataille Flandres Dunkerque, Rennes 35043, France; Inserm UMR991, Rennes, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Crouzet
authors.affiliation: Department of Medical Oncology, Centre Eugène Marquis, Av de la bataille Flandres Dunkerque, Rennes 35043, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Pracht
authors.affiliation: Department of Nuclear Medicine, Centre Eugène Marquis, Av de la bataille Flandres Dunkerque, Rennes 35043, France; Inserm UMR991, Rennes, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lepareur
authors.affiliation: Inserm UMR991, Rennes, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Clément
authors.affiliation: Department of Nuclear Medicine, Centre Eugène Marquis, Av de la bataille Flandres Dunkerque, Rennes 35043, France; Inserm UMR991, Rennes, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Garin
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D059248:Chemoradiotherapy / Q000379:methods; D018281:Cholangiocarcinoma / Q000473:pathology / Q000628:therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004357:Drug Synergism; D006801:Humans; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D017239:Paclitaxel / Q000008:administration & dosage*; D010671:Phenylurea Compounds / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage*; D011836:Radiation Tolerance / Q000187:drug effects; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D000077157:Sorafenib; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D010671:Phenylurea Compounds; D011725:Pyridines; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; C431073:oxiplatin; D003841:Deoxycytidine; D009536:Niacinamide; D000077157:Sorafenib; D017239:Paclitaxel; D000093542:Gemcitabine