Sanguinarine inhibits epithelial ovarian cancer development via regulating long non-coding RNA CASC2-EIF4A3 axis and/or inhibiting NF-κB signaling or PI3K/AKT/mTOR pathway.

This study aimed to investigate the antitumor effects and possible regulatory mechanisms of sanguinarine in epithelial ovarian cancer. 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. 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. 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.

Zhang S ，Leng T ，Zhang Q ，Zhao Q ，Nie X ，Yang L ... -  《-》

[Effects of PI3K/Akt/NF-κB signal pathway on FSH facilitation on cell proliferation and invasion by human epithelial ovarian cancer].

Xu CL ，Lu XL ，Yan XN ，Wang HL ，Chen SQ ... -  《-》

The PI3K/AKT/mTOR pathway is a potential predictor of distinct invasive and migratory capacities in human ovarian cancer cell lines.

Bai H ，Li H ，Li W ，Gui T ，Yang J ，Cao D ，Shen K ... -  《Oncotarget》

Fuzheng Jiedu Decoction Induces Apoptosis and Enhances Cisplatin Efficacy in Ovarian Cancer Cells In Vitro and In Vivo through Inhibiting the PI3K/AKT/mTOR/NF-κB Signaling Pathway.

This study is aimed at investigating the anticancer activity of Fuzheng Jiedu decoction (FJD) alone or in combination with cisplatin in ovarian cancer (OC) models, as well as its underlying mechanisms of action. The anticancer activities of FJD, cisplatin, and the combination of the PI3K inhibitor (LY294002, LY) or activator (IGF-1) were evaluated in OC cell lines in vitro and in a SKOV3 xenograft mouse model in vivo. The cell proliferation and invasion ability were measured using MTT, EdU, and transwell assays, respectively. The cell apoptosis was examined by flow cytometry and JC-1 assays. The expression levels of the Bcl-2 family and the PI3K/AKT/mTOR/NF-κB pathway-related proteins were analyzed by Western blot. The in vivo and in vitro studies showed that FJD administration could significantly inhibit cell proliferation and promote cell apoptosis in two OC cell lines SKOV3 and 3AO and partially decreased the tumor volumes and weights. In addition, FJD could significantly downregulate the protein levels of p-PI3K/PI3K, p-AKT/AKT, p-mTOR/mTOR, NF-κB, p38, and Bcl-2 and upregulate the Bax, Cyt-C, and cleaved caspase-3 in OC tumor tissues and cells. FJD cotreatment increased the efficacy of cisplatin, including inhibiting OC cell proliferation and invasion, promoting cell apoptosis, and inhibiting the PI3K/AKT/mTOR signaling pathway, while this enhancement was suppressed by IGF-1. Similarly, LY also enhanced the anticancer efficacy of cisplatin. This study indicated that FJD could improve the efficacy of cisplatin by inhibiting the PI3K/AKT/mTOR/NF-κB signaling pathway. It is suggested that FJD may be a valuable adjuvant drug for the treatment of OC.

Yang H ，Li H ，Lu S ，Shan S ，Guo Y ... -  《-》

Long noncoding RNA-JPX predicts the poor prognosis of ovarian cancer patients and promotes tumor cell proliferation, invasion and migration by the PI3K/Akt/mTOR signaling pathway.

Li J ，Feng L ，Tian C ，Tang YL ，Tang Y ，Hu FQ ... -  《-》