Hydroxychloroquine Destabilizes Phospho-S6 in Human Renal Carcinoma Cells

摘要: mTOR inhibitors are used to treat metastatic renal cell cancer (RCC), but most patients eventually become resistant. One possible mechanism for resistance is upregulation of autophagy, a pathway that helps recycle intracellular proteins and promotes survival. Hydroxychloroquine (HCQ), potent autophagy inhibitor malaria autoimmune disorders, currently being studied in the context treatment. Here, we have investigated effects HCQ on three different carcinoma derived lines. We found treatment inhibits RCC growth, apoptosis, mitochondrial oxygen consumption, increases rates glycolysis. To understand molecular behind these effects, examined various nodes compared with RAD001. A key downstream readout pathway, phospho-S6 protein, was inhibited by both However, upstream kinase, P70S6K only RAD001 not HCQ, suggesting block P70S6K. Treatment proteasome bortezomib restored levels, reduction caused increased degradation phospho-S6, total S6. Surprisingly, other did exhibit same effects. Our findings suggest causes down-regulation lines via novel shared inhibitors.