Suxian Zhang1, Tianyan Leng1, Qin Zhang1, Qinghua Zhao1, Xiaofeng Nie1, Lihua Yang2. 1. Department of Gynaecology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, China. 2. Department of Gynaecology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, China. Electronic address: lihuazhang33@sina.com.
Abstract
OBJECTIVE: This study aimed to investigate the antitumor effects and possible regulatory mechanisms of sanguinarine in epithelial ovarian cancer. MATERIAL AND METHODS: The effects of sanguinarine on the malignant behaviors of epithelial ovarian cancer SKOV3 cells and the expression of long non-coding RNA CASC2 were investigated. The expression of CASC2 and EIF4A3 in epithelial ovarian cancer tissues and cells were detected, and the potential mechanisms of sanguinarine were explored by investigating the interactions between CASC2 and EIF4A3. Furthermore, the regulatory relationship between sanguinarine and nuclear factor-κB (NF-κB) signaling or PI3K/AKT/mTOR pathway was explored. RESULTS: Sanguinarine exhibited antitumor effects in SKOV3 cells by significantly inhibiting cell viability, migration and invasion and promoting cell apoptosis. Moreover, sanguinarine induced CASC2 expression and silencing of CASC2 reversed the effects of sanguinarine in epithelial ovarian cancer cells. CASC2 was significantly lowly expressed in ovarian cancer tissues and cells, while EIF4A3 was highly expressed. EIF4A3 was identified as a CASC2 binding protein. Knockdown of EIF4A3 reversed the effects of sanguinarine plus CASC2 silencing. Besides, sanguinarine markedly inhibited the activation of NF-κB signaling or PI3K/AKT/mTOR pathway, which was reversed by CASC2 silencing. And the effects of sanguinarine plus CASC2 silencing on the activation of these pathways were further reversed after knockdown of EIF4A3 at the same time. CONCLUSIONS: Our findings reveal that sanguinarine exhibits antitumor effects in epithelial ovarian cancer cells possible via regulating CASC2-EIF4A3 axis and/or inhibiting NF-κB signaling or PI3K/AKT/mTOR pathway. Sanguinarine may serve as a potential therapeutic reagent for epithelial ovarian cancer.
OBJECTIVE: This study aimed to investigate the antitumor effects and possible regulatory mechanisms of sanguinarine in epithelial ovarian cancer. MATERIAL AND METHODS: The effects of sanguinarine on the malignant behaviors of epithelial ovarian cancer SKOV3 cells and the expression of long non-coding RNA CASC2 were investigated. The expression of CASC2 and EIF4A3 in epithelial ovarian cancer tissues and cells were detected, and the potential mechanisms of sanguinarine were explored by investigating the interactions between CASC2 and EIF4A3. Furthermore, the regulatory relationship between sanguinarine and nuclear factor-κB (NF-κB) signaling or PI3K/AKT/mTOR pathway was explored. RESULTS:Sanguinarine exhibited antitumor effects in SKOV3 cells by significantly inhibiting cell viability, migration and invasion and promoting cell apoptosis. Moreover, sanguinarine induced CASC2 expression and silencing of CASC2 reversed the effects of sanguinarine in epithelial ovarian cancer cells. CASC2 was significantly lowly expressed in ovarian cancer tissues and cells, while EIF4A3 was highly expressed. EIF4A3 was identified as a CASC2 binding protein. Knockdown of EIF4A3 reversed the effects of sanguinarine plus CASC2 silencing. Besides, sanguinarine markedly inhibited the activation of NF-κB signaling or PI3K/AKT/mTOR pathway, which was reversed by CASC2 silencing. And the effects of sanguinarine plus CASC2 silencing on the activation of these pathways were further reversed after knockdown of EIF4A3 at the same time. CONCLUSIONS: Our findings reveal that sanguinarine exhibits antitumor effects in epithelial ovarian cancer cells possible via regulating CASC2-EIF4A3 axis and/or inhibiting NF-κB signaling or PI3K/AKT/mTOR pathway. Sanguinarine may serve as a potential therapeutic reagent for epithelial ovarian cancer.