Anti-tumor compound RY10-4 suppresses multidrug resistance in MCF-7/ADR cells by inhibiting PI3K/Akt/NF-κB signaling. (25th December 2017)

• Record Type: Journal Article
• Authors: Yang, Xiaofan; Ding, Yufeng; Xiao, Miao; Liu, Xin; Ruan, Jinlan; Xue, Pingping
• Is Part Of: Chemico-biological interactions. Volume 278(2017)
• Page Start: 22
• Page End: 31
• Publication Date: 2017-12-25
• Subjects: RY10-4 -- Multidrug resistance -- MCF-7/ADR cells -- PI3K/Akt/NF-κB pathway -- P-glycoprotein; MDR multidrug resistance -- ADR adriamycin -- P-gp P-glycoprotein -- ATP adenosine triphosphate -- RF reversal fold -- RTV relative tumor volume -- MFI mean fluorescence intensity; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2017.10.008
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: RY10-4, an anti-tumor agent, exerts cytotoxicity to various human cancer cell lines. However, few studies reported the effect of combined application of RY10-4 and chemotherapeutic drugs against cancer cells with multidrug resistance (MDR). In this study, P-glycoprotein (P-gp), which is reported to mediate MDR to anti-cancer drugs, was proved to be overexpressed in the adriamycin (ADR)-resistant human breast cancer cells, namely MCF-7/ADR cells. Furthermore, RY10-4 application resulted in a downregulation of P-gp in MCF-7/ADR cells, thus leading to higher chemosensitivity to ADR. Our study further demonstrated that the MDR phenomenon was under the control of the PI3K/Akt/NF-κB pathway, which was suppressed by RY10-4, leading to MDR reversal effects in MCF-7/ADR cells. In vivo, MCF-7/ADR cells were effectively suppressed by the combined ADR/RY10-4 treatment compared with the ADR-alone treatment. Taken together, these results demonstrated that RY10-4 reverses the MDR phenotype in MCF-7/ADR cells by suppressing the PI3K/Akt/NF-κB pathway. Highlights: RY10-4 could partially reverse multidrug resistance in MCF-7/ADR cells. PI3K/Akt/NF-κB pathway was involved in the development of MDR in MCF-7/ADR cells. RY10-4 suppressed MDR in MCF-7/ADR cells by inhibiting PI3K/Akt/NF-κB pathway.