Combined treatment with silibinin and either sorafenib or gefitinib enhances their growth-inhibiting effects in hepatocellular carcinoma cells

• Main Authors: Ha Ra Gu, Su Cheol Park, Su Jin Choi, Jae Cheol Lee, You Cheoul Kim, Chul Ju Han, Jin Kim, Ki Young Yang, Yeon Joo Kim, Geum Youb Noh, So Hyeon No, Jae-Hoon Jeong
• Format: Article
• Language: English
• Published: Korean Association for the Study of the Liver 2015-03-01
• Series: Clinical and Molecular Hepatology
• Subjects: Silibinin; Gefitinib; Sorafenib; Hepatocellular carcinoma
• Online Access: http://e-cmh.org/upload/pdf/cmh-21-49.pdf

Background/AimsSilibinin, 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.MethodsSeveral 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.ResultsGefitinib, 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.ConclusionsCombined 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.