title: Induction of fibronectin in response to epidermal growth factor is suppressed by silibinin through the inhibition of STAT3 in triple negative breast cancer cells.
abstract: Fibronectin (FN) plays a major role in cell adhesion, migration and oncogenic transformation. Aberrant FN expression is associated with poor prognosis in various types of cancer, including breast cancer. In this study, we investigated the effect of silibinin on the epidermal growth factor (EGF)-induced FN expression in triple negative breast cancer (TNBC) cells. Our data showed that the levels of FN mRNA and protein expression were dose-dependently increased by EGF in MDA-MB468 and BT20 breast cancer cells. Consequently, EGF-induced FN expression was decreased by the epidermal growth factor receptor (EGFR) inhibitors AG1478 and gefitinib. EGF-induced FN expression was also decreased by MEK1/2, PI3K and STAT3 specific inhibitors. In the present study, we observed for the first time that EGF-induced FN expression was significantly decreased by silibinin treatment in TNBC cells. Furthermore, we found that silibinin suppressed the EGF-induced phosphorylation of STAT3 but not Erk and Akt. Taken together, silibinin downregulated EGF-induced FN expression through the inhibition of STAT3 phosphorylation in TNBC cells. Silibinin may be a promising anticancer drug for the treatment of TNBC.
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea.
authors.forename: Sangmin
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea.
authors.forename: Myeongjin
authors.initials: M
authors.lastname: Jeon
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea.
authors.forename: Jeongmin
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea.
authors.forename: Jeonghun
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea.
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Oh
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea.
authors.forename: Taewoo
authors.initials: T
authors.lastname: Jung
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea.
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Nam
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea.
authors.forename: Won Ho
authors.initials: WH
authors.lastname: Kil
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea.
authors.forename: Jeong Eon
authors.initials: JE
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005260:Female; D005353:Fibronectins / Q000235:genetics* / Q000378:metabolism*; D000077156:Gefitinib; D006801:Humans; D061986:MCF-7 Cells; D010766:Phosphorylation; D011799:Quinazolines / Q000494:pharmacology; D015398:Signal Transduction; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D005353:Fibronectins; D011799:Quinazolines; D012838:Silymarin; D020032:Tyrphostins; C101044:RTKI cpd; D000077385:Silybin; D000077156:Gefitinib