Tranilast-induced stress alleviation in solid tumors improves the efficacy of chemo- and nanotherapeutics in a size-independent manner

• DOI: 10.1038/srep46140
• Publication Date: 2017-04-10T09:20:36Z
• Authors: Panagiotis Papage...; Christiana Polydorou; Fotios Mpekris; Chrysovalantis Vo...; Eliana Agathokleous; Constantina P. Ka...; Triantafyllos Sty...
• Keywords: Tranilast; Desmoplasia

Abstract Accumulation of mechanical stresses during cancer progression can induce blood and lymphatic vessel compression, creating hypo-perfusion, hypoxia interstitial hypertension which decrease the efficacy chemo- nanotherapies. Stress alleviation treatment has been recently proposed to reduce in order decompress tumor vessels improve perfusion chemotherapy. However, it remains unclear if improves nanomedicines, present numerous advantages over traditional chemotherapeutic drugs. Furthermore, we need identify safe well-tolerated pharmaceutical agents that stress levels may be added patients’ regimen. Here, show mathematically with a series vivo experiments delivery drugs size-independent manner. Importantly, propose repurposing tranilast, clinically approved anti-fibrotic drug as stress-alleviating agent. Using two orthotopic mammary models, demonstrate tranilast reduces stresses, decreases fluid pressure (IFP), significantly enhances different-sized drugs, doxorubicin, Abraxane Doxil, by suppressing TGFβ signaling expression extracellular matrix components. Our findings strongly suggest could directly used promising strategy enhance, not only chemotherapy, but also nanomedicine.