Sildenafil triggers tumor lethality through altered expression of HSP90 and degradation of PKD2

摘要: The repurposing of existing drugs has emerged as an attractive additional strategy to the development novel compounds in fight against cancerous diseases. Inhibition phosphodiesterase 5 (PDE5) been claimed a potential approach target various cancer subtypes recent years. However, data on treatment tumors with PDE5 inhibitors well underlying mechanisms are yet very scarce. Here, we report that tumor cells low concentrations Sildenafil was associated decreased cell proliferation and augmented apoptosis vitro resulted impaired growth vivo. Notably, incubation altered expression HSP90 chaperone followed by degradation protein kinase D2, client previously reported be involved growth. Furthermore, involvement doses PU-H71, inhibitor currently under clinical evaluation, combination Sildenafil, synergistically negatively impacted viability Taken together, our study suggests already approved drugs, alone or oncology-dedicated compounds, may represent therapeutic strategy.