Overexpression of RSK4 reverses doxorubicin resistance in human breast cancer cells via PI3K/Akt signaling pathway

2020 
Doxorubicin is one of the most effective chemotherapy drugs for the treatment of metastatic breast cancer, but drug resistance becomes an obstacle to treatment. This study aims to investigate the role of Ribosomal S6 protein kinase 4 (RSK4) in regulating breast cancer (BC) resistance to doxorubicin (DOX). We first used Kaplan-Meier Plotter to identify the prognostic roles of RSK4 in BC. Doxorubicin resistant breast cancer cells (MCF-7/DOX) were constructed and the expression of RSK4 was determined by RT-PCR 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, breast cancer resistance protein. Effects of RSK4 on activation of the PI3K/AKT signaling pathway were also tested. Furthermore, tumor xenograft in nude mice was constructed to observe the effect of RSK4 overexpression on tumor growth in vivo. In conclusion, RSK4 was positively correlated with survival rate in breast cancer patients, which is lowly expressed in MCF-7/DOX. Meanwhile, the overexpression of RSK4 may inhibit drug resistance, cell migration, invasion, apoptosis and tumor growth. RSK4 may effectively attenuate DOX resistance in BC by inhibiting the PI3K/AKT signaling pathway.
    • Correction
    • Source
    • Cite
    • Save
    • Machine Reading By IdeaReader
    37
    References
    5
    Citations
    NaN
    KQI
    []