The cdk1-cyclin B complex is involved in everolimus triggered resistance in the PC3 prostate cancer cell line

The growth potential of PC3 prostate cancer cells, sensible (PC3par) or resistant (PC3res) to the mTOR inhibitor everolimus (RAD001) was investigated. Cell growth and proliferation of PC3res was similar to that of PC3par, and late apoptosis increased in PC3par but decreased in PC3res following treatment with low dosed everolimus. PC3res accumulated in the G2/M-phase, accompanied by cdk1, cdk2 and cyclin B elevation. Knocking down cdk1 or cyclin B distinctly blocked the growth activity of PC3res. One reason for everolimus resistance may be up-regulation of the cdk1-cyclin B complex in prostate cancer cells, leading to enhanced progression towards G2/M.

► Resistance to the mTOR-inhibitor everolimus was established in prostate cancer cells.
► Resistance led to accumulation of the cells in the G2/M-phase.
► Cdk1 and cyclin B were elevated in the resistant cells.
► Down-regulation of cyclin B restored the tumor cell sensitivity to everolimus.