title: Antiproliferative effects of sorafenib and pegylated IFN‑α2b on human liver cancer cells in vitro and in vivo.
abstract: Novel therapeutic strategies are needed to treat patients with advanced hepatocellular carcinoma (HCC). Combination therapy of sorafenib and type I interferon (IFN) has substantial activity in patients with metastatic renal cell carcinoma. We investigated the antiproliferative effects of sorafenib in combination with pegylated interferon-α2b (PEG-IFN-α2b) on human hepatocellular carcinoma (HCC) cells in vitro and in vivo. A poorly differentiated HCC cell line derived from a patient with hepatitis C virus infection, HAK-1B and the moderately differentiated HCC cell line KIM-1 were used in this study. We demonstrated a synergistic antiproli-ferative effect of combination therapy on HAK-1B cells in vitro. In the in vivo study, a significant reduction of tumor volume and weight were observed in the combination group in both HAK-1B and KIM1 tumors, although synergistic effects were not clearly observed. The density of CD34‑positive microvessels was significantly lower and cleaved caspase‑3-positive apoptotic cell numbers were higher, in the sorafenib group and the combination group compared to the control or PEG-IFN-α2b group in both HAK-1B and KIM-1 tumors. Ki67 labeling index was significantly lower in the combination group compared to the control group in KIM-1 tumors. In conclusion, our results suggest that the combination therapy may be more effective for the treatment of HCC cases with variable sensitivity to antitumor effects of single therapy with either sorafenib or PEG-IFN-α2b.
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Japan. kusano_hironori@kurume-u.ac.jp
authors.forename: Hironori
authors.initials: H
authors.lastname: Kusano
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ogasawara
authors.forename: Jun
authors.initials: J
authors.lastname: Akiba
authors.forename: Masamichi
authors.initials: M
authors.lastname: Nakayama
authors.forename: Kosuke
authors.initials: K
authors.lastname: Ueda
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Yano
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D055806:Microvessels / Q000187:drug effects; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D000077157:Sorafenib
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D010671:Phenylurea Compounds; D011994:Recombinant Proteins; D009536:Niacinamide; D011092:Polyethylene Glycols; D000077157:Sorafenib; D053148:Caspase 3; C417083:peginterferon alfa-2b