title: Combined treatment with silibinin and either sorafenib or gefitinib enhances their growth-inhibiting effects in hepatocellular carcinoma cells.
abstract: OBJECTIVE
  Silibinin, the main component of silymarin, is used as a hepatoprotectant and exhibits anticancer effects against various cancer cells. This study evaluated the effects of a combination of silibinin with either gefitinib or sorafenib on hepatocellular carcinoma (HCC) cells.
  
  
  METHODS
  Several different human HCC cell lines were used to test the growth-inhibiting effects and cell toxicity of silibinin both alone and in combination with either gefitinib or sorafenib. The cell viability and growth inhibition were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, trypan blue staining, and a colony-forming assay. Furthermore, changes in epidermal growth factor receptor (EGFR)-related signals were evaluated by Western blot analysis.
  
  
  RESULTS
  Gefitinib, sorafenib, and silibinin individually exhibited dose-dependent antiproliferative effects on HCC cells. Combined treatment with silibinin enhanced the gefitinib-induced growth-inhibiting effects in some HCC cell lines. The combination effect of gefitinib and silibinin was synergistic in the SNU761 cell line, but was only additive in the Huh-BAT cell line. The combination effect may be attributable to inhibition of EGFR-dependent Akt signaling. Enhanced growth-inhibiting effects were also observed in HCC cells treated with a combination of sorafenib and silibinin.
  
  
  CONCLUSIONS
  Combined treatment with silibinin enhanced the growth-inhibiting effects of both gefitinib and sorafenib. Therefore, the combination of silibinin with either sorafenib or gefitinib could be a useful treatment approach for HCC in the future.
authors.affiliation: Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Korea.
authors.forename: Ha Ra
authors.initials: HR
authors.lastname: Gu
authors.affiliation: Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Korea.
authors.forename: Su Cheol
authors.initials: SC
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Korea.
authors.forename: Jae Cheol
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Korea.
authors.forename: You Cheoul
authors.initials: YC
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Korea.
authors.forename: Chul Ju
authors.initials: CJ
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Korea.
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Korea.
authors.forename: Yeon Joo
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Korea.
authors.forename: Geum Youb
authors.initials: GY
authors.lastname: Noh
authors.affiliation: Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences, Seoul, Korea. ; Department of Radiological Cancer Medicine, University of Science and Technology, Seoul, Korea.
authors.forename: So Hyeon
authors.initials: SH
authors.lastname: No
authors.affiliation: Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences, Seoul, Korea. ; Department of Radiological Cancer Medicine, University of Science and Technology, Seoul, Korea.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Jeong
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D066246:ErbB Receptors / Q000378:metabolism; D000077156:Gefitinib; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D011799:Quinazolines; D012838:Silymarin; D009536:Niacinamide; D000077385:Silybin; D000077157:Sorafenib; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D000077156:Gefitinib
keywords: Gefitinib; Hepatocellular carcinoma; Silibinin; Sorafenib
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