Repurposing paclitaxel for the treatment of fibrosis: indication discovery for existing drugs

Abstract

Xiao-Wu Chen,1 Wei Duan,2 Shu-Feng Zhou31Department of General Surgery, The First People’s Hospital of Shunde, Southern Medical University, Shunde, Foshan, Guangdong, People’s Republic of China; 2School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia; 3Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, FL, USAIn the recently published paper by Zhang et al1 in Drug Des Develop Ther, the authors have evaluated the role of signal transducer and activator of transcription 3 (STAT3) in the antifibrotic activity of paclitaxel in vitro and in mice. They have reported that the treatment of paclitaxel at 2–4 μM reduced the level of phosphorylated STAT3 at Tyr705 in a dose- and time-dependent manner, and downregulated the expression of fibronectin, α-smooth muscle actin (α-SMA), and collagen I in cultured rat renal interstitial fibroblast NRK-49F cells derived from normal kidney. Treatment of the cells with the selective STAT3 inhibitor S3I-201 at 50 mM suppressed the expression of fibronectin, α-SMA, and collagen I in NRK-49F cells. However, S3I-201 treatment increased the expression of phosphorylated STAT1 but did not affect that of phosphorylated STAT5M. The immunoprecipitation assay has revealed that paclitaxel inhibited the STAT3 activity by disrupting the binding of STAT3 with tubulin independently of the effect on STAT3 phosphorylation and by inhibiting STAT3 nucleus translocation.1