Inhibition of Nek2 by Small Molecules Affects Proteasome Activity
Figure 6
The combination of bortezomib and Nek2 inhibitors reduces proteasome activity to a greater extent than either drug alone. (a) The combination of bortezomib with either HCI-2184 or HCI-2389 significantly increased the effectiveness of bortezomib on Nek2-OE HeLa cells compared to GFP-transfected controls. (b) The combination of Nek2 inhibitors HCI-2184 or HCI-2389 and bortezomib inhibited proteasome activity in Nek2-OE HeLa cells to a greater extent than either drug alone. (c) and (d), the combination of Bortezomib and HCI-2389 decreased proteasome activity compared to untreated or DMSO treated H929 (c) or KMS28PE (d) cells treated with either empty vector (control) or Nek2 overexpressing (+Nek2) cells. (e), the combination of bortezomib and HCI-2389 decreased proteasome activity in empty vector (control), Nek2 plasmid (+Nek2), and Nek2 siRNA knockdown (−Nek2) ARP1 cells. The combination also resulted in a significant decrease in proteasome activity in ARP1 cells resistant to bortezomib (ARP1 resistant). For (a) and (c)–(e), , , .
