ritonavir and ixazomib

There is no curative treatment for advanced bladder cancer. Causing ubiquitinated protein accumulation and endoplasmic reticulum stress is a novel approach to cancer treatment. The HIV protease inhibitor ritonavir has been reported to suppress heat shock protein 90 and increase the amount of unfolded proteins in the cell. If the proteasome functions normally, however, they are rapidly degraded. We postulated that the novel proteasome inhibitor ixazomib combined with ritonavir would kill bladder cancer cells effectively by inhibiting degradation of these unfolded proteins and thereby causing ubiquitinated proteins to accumulate. The combination of ritonavir and ixazomib induced drastic apoptosis and inhibited the growth of bladder cancer cells synergistically. The combination decreased the expression of cyclin D1 and cyclin-dependent kinase 4, and increased the sub-G

Topics: Acetylation; Antineoplastic Agents; Apoptosis; Boron Compounds; Cell Line, Tumor; Cyclin D1; Cyclin-Dependent Kinase 4; Drug Synergism; Endoplasmic Reticulum Stress; Glycine; Humans; Proteasome Inhibitors; Ritonavir; Ubiquitinated Proteins; Ubiquitination; Urinary Bladder Neoplasms