Kim Sangmin, Jeon Myeongjin, Lee Jeongmin, Han Jeonghun, Oh Soo-Jin, Jung Taewoo, Nam Seok Jin, Kil Won Ho, Lee Jeong Eon
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea.
Oncol Rep. 2014 Nov;32(5):2230-6. doi: 10.3892/or.2014.3450. Epub 2014 Aug 29.
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.
纤连蛋白（FN）在细胞黏附、迁移和致癌转化中起主要作用。FN表达异常与包括乳腺癌在内的多种癌症的不良预后相关。在本研究中，我们研究了水飞蓟宾对三阴性乳腺癌（TNBC）细胞中表皮生长因子（EGF）诱导的FN表达的影响。我们的数据表明，在MDA-MB468和BT20乳腺癌细胞中，EGF可使FN mRNA和蛋白表达水平呈剂量依赖性增加。因此，表皮生长因子受体（EGFR）抑制剂AG1478和吉非替尼可降低EGF诱导的FN表达。MEK1/2、PI3K和STAT3特异性抑制剂也可降低EGF诱导的FN表达。在本研究中，我们首次观察到水飞蓟宾处理可显著降低TNBC细胞中EGF诱导的FN表达。此外，我们发现水飞蓟宾可抑制EGF诱导的STAT3磷酸化，但不抑制Erk和Akt。综上所述，水飞蓟宾通过抑制TNBC细胞中STAT3磷酸化下调EGF诱导的FN表达。水飞蓟宾可能是一种有前景的治疗TNBC的抗癌药物。
