Combined treatment with silibinin and either sorafenib or gefitinib enhances their growth-inhibiting effects in hepatocellular carcinoma cells.
- Author:
Ha Ra GU
1
;
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
Author Information
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords: Silibinin; Gefitinib; Sorafenib; Hepatocellular carcinoma
- MeSH: Antineoplastic Agents/*pharmacology; Carcinoma, Hepatocellular/metabolism/pathology; Cell Line, Tumor; Cell Proliferation/*drug effects; Cell Survival/drug effects; Down-Regulation/drug effects; Drug Screening Assays, Antitumor; Drug Synergism; Humans; Liver Neoplasms/metabolism/pathology; Niacinamide/*analogs & derivatives/pharmacology; Phenylurea Compounds/*pharmacology; Proto-Oncogene Proteins c-akt/metabolism; Quinazolines/*pharmacology; Receptor, Epidermal Growth Factor/metabolism; Signal Transduction/drug effects; Silymarin/*pharmacology
- From:Clinical and Molecular Hepatology 2015;21(1):49-59
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND/AIMS: 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.
