Physcion-8-O-β-d-glucoside interferes with the nuclear factor-κB pathway and downregulates P-glycoprotein expression to reduce paclitaxel resistance in ovarian cancer cells

• Published in: Journal of pharmacy and pharmacology 2021-03, Vol.73 (4), p.545-552
• Main Authors: Li, Xue, He, Yuanqi, Wei, Liqun, Zhang, Jianzhong, Li, Xiaoxiao, Cui, Weiwei, Zhang, Shihong
• Format: Article
• Language: English
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1093/jpp/rgaa025

Abstract Objective This study assessed whether physcion-8-O-beta-D-monoglucoside (PG) sensitises paclitaxel (PTX)-resistant ovarian cancer cells and explored the underlying mechanism. Methods Ovarian cancer SK-OV-3 cells were used to establish PTX-resistant SK-OV-3 (SK-OV-3/PTX) cells. The Cell Counting Kit-8 assay and crystal violet staining were used to determine cell viability. P-glycoprotein (P-gp) and nuclear factor (NF)-κB expression and cell distributions were detected using immunofluorescence. Cell apoptosis and protein expression changes were detected using flow cytometry and western blotting, respectively. Effect of PG in vivo was evaluated using a xenograft tumour model. P-gp expression in tumour tissues was detected using immunohistochemical staining. Key findings PG (1–10 μm) did not significantly affect SK-OV-3/PTX cell proliferation but significantly downregulated P-gp expression. PG pretreatment (1–10 μm) enhanced PTX cytotoxicity. PG treatment decreased the quantity of phosphorylated-NF-κB p65 in SK-OV-3/PTX cell total proteins and upregulated IKBα expression. Simultaneously, it decreased NF-κB p65 levels in nuclear proteins. PG (1–10 μm) inhibited NF-κB p65 entry into the nucleus. PTX plus PG significantly inhibited SK-OV-3/PTX xenograft tumour growth. PG (1–10 μm) reduced P-gp expression in transplanted tumour tissue. Conclusions PG can enhance the sensitivity of PTX-resistant ovarian cancer cells SK-OV-3/PTX to PTX, and this effect is related to inhibiting NF-κB from entering the nucleus and down-regulating the expression of P-gp protein.