EGFR 신호전달과정의 조절을 통한 실리카 나노입자의 인간 유방암 세포에 대한 세포독성효과

Abstract

Silica nanoparticles are broadly used in many industrial areas such as cosmetics and drugs. However, some reports have described cytotoxicity of silica nanoparticles, while others have reported the opposite. Herein, I found that silica nanoparticles had a cytotoxicity in MDA-MB-231 and Hs578T breast cancer cells via modulation of Epidermal Growth Factor Receptor (EGFR) signaling cascades. EGFR, a member of the ErbB family of receptors, activates its downstream signaling cascades with homo- or hetero-dimerization with other ErbB family receptors and subsequent auto-phosphorylation. I found that treatment with silica nanoparticles modulated the growth and survival of breast cancer cell lines MDA-MB-231 and Hs578T. I also detected reduced cell motility and an increase of the apoptotic cell fraction after exposure to silica nanoparticles. In line with these findings, I investigated the effect of silica nanoparticles on intracellular signaling cascades elicited by EGFR. Exposure to silica nanoparticles remarkably repressed the dimerization of EGFR, followed by downregulation of its downstream c-Src and STAT3 signaling cascades. I propose that silica nanoparticles can act as an inhibitor of EGFR dimerization and exert a cytotoxicity by modulation of EGFR signaling in breast cancer cells.