ArticleCellular oncology (Dordrecht, Netherlands)2021
Raloxifene inhibits pancreatic adenocarcinoma growth by interfering with ERβ and IL-6/gp130/STAT3 signaling.
Article in Cellular oncology (Dordrecht, Netherlands), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 26 citations in OpenAlex.
- Article
- Integrative transcriptomic profiling reveals NK cell exhaustion-associated prognostic genes and identifies CSF1 as a key immunoregulatory target in hepatocellular carcinoma.Biology direct · 2026Article
- Estradiol and Raloxifene Protect Ovariectomized Mice from Acute Kidney Injury via G Protein-Coupled Estrogen Receptor-Mediated Nuclear Factor Erythroid 2-Related Factor 2/Heme Oxygenase-1 Activation.International journal of molecular sciences · 2026Article
- Estrogen Production in Pancreatic Cancer Shapes a Tumor-Suppressive Stromal Microenvironment.Cancer research · 2026Article
- Rethinking estrogen receptor β in EAOC: a synergistic modulator in a genomically informed landscape.Journal of ovarian research · 2026Review
- Multicomplex Pharmacophore Modeling of Estrogen Receptors Suggests the Probable Repurposing of Procaterol as an Antiproliferative Agent Against Breast Cancer Cells.International journal of molecular sciences · 2026Article
- Mechanistic insights into hepatic metastasis of pancreatic cancer: molecular perspectives.Translational gastroenterology and hepatology · 2026Review
- Harnessing the power of cancer-associated fibroblasts to revolutionize pancreatic cancer treatment.Cancer biology & medicine · 2025Review
- Article
- An in-silico scaffold- hopping approach to design novel inhibitors against gp130: A potential therapeutic application in cancer and Covid-19.Molecular diversity · 2024Article
- Estrogen Signals through ERβ in Breast Cancer; What We Have Learned since the Discovery of the Receptor.Receptors (Basel, Switzerland) · 2024Article
- Investigation of the potential effects of estrogen receptor modulators on immune checkpoint molecules.Scientific reports · 2024Article
- Inhibition of gp130 alleviates LPS-induced lung injury by attenuating apoptosis and inflammation through JAK1/STAT3 signaling pathway.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- Targeting Interleukin-6/Glycoprotein-130 Signaling by Raloxifene or SC144 Enhances Paclitaxel Efficacy in Pancreatic Cancer.Cancers · 2023Article
- Gp130 is expressed in pancreatic cancer and can be targeted by the small inhibitor molecule SC144.Journal of cancer research and clinical oncology · 2023Article
- Betulinic acid-mediating miRNA-365 inhibited the progression of pancreatic cancer.Oncology research · 2023Article
- Potentiality of raloxifene loaded melittin functionalized lipidic nanovesicles against pancreatic cancer cells.Drug delivery · 2022Article
- Thymidine phosphorylase induction by ionizing radiation antagonizes 5-fluorouracil resistance in human ductal pancreatic adenocarcinoma.Radiation and environmental biophysics · 2022Article
- Role of estrogen receptors in health and disease.Frontiers in endocrinology · 2022Review
- Estrogen Receptor Modulators in Viral Infections Such as SARS-CoV-2: Therapeutic Consequences.International journal of molecular sciences · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
purposeCurrently, the exact role of estrogen receptor (ER) signaling in pancreatic cancer is unknown. Recently, we showed that expression of phosphorylated ERβ correlates with a poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). Here, we hypothesized that raloxifene, a FDA-approved selective ER modulator (SERM), may suppress PDAC tumor growth by interfering with ERβ signaling. To test this hypothesis, we studied the impact of raloxifene on interleukin-6/glycoprotein-130/signal transducer and activator of transcription-3 (IL-6/gp130/STAT3) signaling.
methodsHuman PDAC cell lines were exposed to raloxifene after which growth inhibition was assessed using a BrdU assay. ER knockdown was performed using siRNAs specific for ERα and ERβ. The effects of raloxifene on IL-6 expression and STAT3 phosphorylation in PDAC cells were assessed by ELISA and Western blotting, respectively. In addition, raloxifene was administered to an orthotopic PDAC tumor xenograft mouse model, after which tumor growth was monitored and immunohistochemistry was performed.
resultsRaloxifene inhibited the in vitro growth of PDAC cells, and this effect was reversed by siRNA-mediated knockdown of ERβ, but not of ERα, indicating ER isotype-specific signaling. We also found that treatment with raloxifene inhibited the release of IL-6 and suppressed the phosphorylation of STAT3
conclusionsInhibition of ERβ and the IL-6/gp130/STAT3 signaling pathway by raloxifene leads to potent reduction of PDAC growth in vitro and in vivo. Our results suggest that ERβ signaling and IL-6/gp130 interaction may serve as promising drug targets for pancreatic cancer and that raloxifene may serve as an attractive therapeutic option for PDAC patients expressing the ERβ isotype.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.