Doxorubicin (DOX) is one of the most effective chemotherapy drugs for the treatment of metastatic breast cancer (BC), but drug resistance becomes an obstacle to treatment. This study aims to investigate the role of Ribosomal S6 protein kinase 4 (RSK4) in regulating BC resistance to DOX. We first used Kaplan-Meier Plotter to identify the prognostic roles of RSK4 in BC. DOX-resistant BC cells (MCF-7/DOX) were constructed and the expression of RSK4 was determined by reverse transcript polymerase chain reaction and western blot. Subsequently, we overexpressed the RSK4 in MCF-7/DOX cells, and measured drug resistance, colony formation, cell migration, invasion ability and cell apoptosis after transfection. In addition, western blot was used to explore the expression of apoptosis-related proteins and BC-resistance protein. Effects of RSK4 on activation of the PI3K/AKT signalling pathway were also tested. Furthermore, tumour xenograft in nude mice was constructed to observe the effect of RSK4 overexpression on tumour growth in vivo. In conclusion, RSK4 was positively correlated with survival rate in BC patients, which is lowly expressed in MCF-7/DOX. Meanwhile, the overexpression of RSK4 may inhibit drug resistance, cell migration, invasion, apoptosis and tumour growth. RSK4 may effectively attenuate DOX resistance in BC by inhibiting the PI3K/AKT signalling pathway.
Keywords: PI3K/AKT signalling pathway; RSK4; breast cancer; doxorubicin; drug-resistance.
© The Author(s) 2020. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.