Conclusions
HDAC inhibition induced a strong response of temsirolimus-resistant bladder cancer cells. Therefore, the temsirolimus-VPA-combination might be an innovative strategy for bladder cancer treatment.
Methods
Parental (par) and resistant (res) RT112 and UMUC-3 cells were exposed to the HDAC inhibitor VPA. Tumor cell growth, proliferation, cell cycling and expression of cell cycle regulating proteins were then evaluated. siRNA blockade was used to investigate the functional impact of the proteins. Conclusions: HDAC inhibition induced a strong response of temsirolimus-resistant bladder cancer cells. Therefore, the temsirolimus-VPA-combination might be an innovative strategy for bladder cancer treatment.
Results
The HDAC inhibitor valproic acid (VPA) significantly inhibited growth, proliferation and caused G0/G1 phase arrest in RT112res and UMUC-3res. cdk1, cyclin B, cdk2, cyclin A and Skp1 p19 were down-regulated, p27 was elevated. Akt-mTOR signaling was deactivated, whereas acetylation of histone H3 and H4 in RT112res and UMUC-3res increased in the presence of VPA. Knocking down cdk2 or cyclin A resulted in a significant growth blockade of RT112res and UMUC-3res. Materials and methods: Parental (par) and resistant (res) RT112 and UMUC-3 cells were exposed to the HDAC inhibitor VPA. Tumor cell growth, proliferation, cell cycling and expression of cell cycle regulating proteins were then evaluated. siRNA blockade was used to investigate the functional impact of the proteins. Conclusions: HDAC inhibition induced a strong response of temsirolimus-resistant bladder cancer cells. Therefore, the temsirolimus-VPA-combination might be an innovative strategy for bladder cancer treatment.