Raloxifene inhibits pancreatic adenocarcinoma growth by interfering with ERβ and IL-6/gp130/STAT3 signaling

• DOI: 10.1007/s13402-020-00559-9
• Publication Date: 2020-09-17T14:06:27Z
• Authors: Ioannis Pozios; Nina N. Seel; Nina A. Hering; Lisa Hartmann; Verena Liu; Peter Camaj; Mario H. Müller; Lucas D. Lee; Christiane J. Bruns; Martin E. Kreis; Hendrik Seeliger
• Keywords: Raloxifene

Abstract Purpose Currently, the exact role of estrogen receptor (ER) signaling in pancreatic cancer is unknown. Recently, we showed that expression phosphorylated ERβ correlates with a poor prognosis patients ductal adenocarcinoma (PDAC). Here, hypothesized raloxifene, FDA-approved selective ER modulator (SERM), may suppress PDAC tumor growth by interfering signaling. To test this hypothesis, studied impact raloxifene on interleukin-6/glycoprotein-130/signal transducer and activator transcription-3 (IL-6/gp130/STAT3) Methods Human cell lines were exposed to after which inhibition was assessed using BrdU assay. knockdown performed siRNAs specific for ERα ERβ. The effects IL-6 STAT3 phosphorylation cells ELISA Western blotting, respectively. In addition, administered an orthotopic xenograft mouse model, monitored immunohistochemistry performed. Results Raloxifene inhibited vitro cells, effect reversed siRNA-mediated ERβ, but not ERα, indicating isotype-specific We also found treatment release suppressed Y705 cells. vivo, growth, lymph node liver metastases as well Ki-67 reduced mice treated raloxifene. Conclusions Inhibition IL-6/gp130/STAT3 pathway leads potent reduction vivo. Our results suggest IL-6/gp130 interaction serve promising drug targets attractive therapeutic option expressing isotype.