Osthole Suppresses Prostate Cancer Progression by Modulating PRLR and the JAK2/STAT3 Signaling Axis

Yan, L.; He, Y.; Cui, Q.; Wang, X.; Lv, F.; Cao, K.; Shao, Y.

doi:10.1101/2024.12.30.630802

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bioRxiv · 10.1101/2024.12.30.630802

Osthole Suppresses Prostate Cancer Progression by Modulating PRLR and the JAK2/STAT3 Signaling Axis

Yan, L.·He, Y.·Cui, Q.·Wang, X.·Lv, F.·Cao, K.·Shao, Y.

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Abstract

Prostate cancer is a common malignancy in men with limited effective treatment options, highlighting the urgent need for novel therapeutic approaches. Osthole, a natural coumarin compound with antitumor properties, has demonstrated potential in targeting various cancers. This study investigates the therapeutic effects of Osthole in prostate cancer by focusing on its ability to target the Prolactin Receptor (PRLR) and modulate the JAK2/STAT3 signaling pathway. Using a combination of network pharmacology, in vitro assays, and in vivo experiments, we first employed network pharmacology to predict Ostholes potential targets, identifying 68 targets shared with prostate cancer, including AKT1, TNF, IL6, STAT3, and CTNNB1. We then confirmed these targets and assessed the effects of Osthole on cell proliferation, migration, and apoptosis using the Cell Counting Kit-8 (CCK-8) and transwell invasion assays. To further elucidate the molecular interactions and protein expression levels, we employed molecular docking and western blot analysis. Our findings revealed that Osthole significantly inhibited prostate cancer cell proliferation and migration in a dose-dependent manner and reduced tumor volume in in vivo assays. Western blot analysis also indicated that Osthole downregulated PRLR expression and decreased the phosphorylation of JAK2 and STAT3, suggesting the inhibition of the JAK2/STAT3 pathway. These results collectively highlight the therapeutic potential of Osthole in targeting prostate cancer cells through PRLR and modulating the JAK2/STAT3 pathway, warranting further clinical exploration.

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Yan, L., He, Y., Cui, Q., Wang, X., Lv, F., Cao, K., Shao, Y.. 2024-12-31. Osthole Suppresses Prostate Cancer Progression by Modulating PRLR and the JAK2/STAT3 Signaling Axis. https://doi.org/10.1101/2024.12.30.630802

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