Inhibition of Galectin-1 and androgen receptor axis enhances enzalutamide treatment in enzalutamide resistant prostate cancer

Inhibition of Galectin-1 and androgen receptor axis enhances enzalutamide treatment in enzalutamide resistant prostate cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Inhibition of Galectin-1 and androgen receptor axis enhances enzalutamide treatment in enzalutamide resistant prostate cancer Tsung-Chieh Shih This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5389794/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Prostate cancer (PCa) remains a prevalent and deadly disease, particularly in its advanced stages. Despite various available treatments, resistance to drugs like enzalutamide continues to present significant challenges. This study demonstrated the significant upregulation of Galectin-1 (Gal-1) in enzalutamide-resistant PCa cells. Specific siRNA-mediated knockdown of Gal-1 inhibited proliferation in enzalutamide-resistant prostate cancer cells and resensitized them to enzalutamide treatment in an orthotopic mouse model. Elevated levels of androgen receptor full length and AR-V7 are key mechanisms underlying resistance to enzalutamide in PCa. Our findings showed that Gal-1 knockdown suppressed AR and AR-V7 expression and their transcriptional activity. In addition, pharmacological targeting of Gal-1 using LLS30 significantly suppressed the growth of enzalutamide-resistant PCa cells and exhibited synergistic effects when combined with enzalutamide. Notably, this combination significantly inhibited the growth of enzalutamide-resistant xenografts in vivo. Furthermore, RNA-seq analysis further revealed that LLS30 modulates AR and AR-V7 signaling through the inhibition of associated target genes. These findings highlighted Gal-1 as a promising therapeutic target for combating enzalutamide resistance in PCa. Importantly, targeting the Gal-1/AR/AR-V7 axis with LLS30 emerges as a promising strategy to enhance the efficacy of enzalutamide treatment and address enzalutamide resistance in PCa. Translational Medicine Prostate cancer Galectin-1 LLS30 Full Text Additional Declarations The authors declare potential competing interests as follows: Author Dr. Shih and Hsiao-Chi Wang are employed by Kibio Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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Despite various available treatments, resistance to drugs like enzalutamide continues to present significant challenges. This study demonstrated the significant upregulation of Galectin-1 (Gal-1) in enzalutamide-resistant PCa cells. Specific siRNA-mediated knockdown of Gal-1 inhibited proliferation in enzalutamide-resistant prostate cancer cells and resensitized them to enzalutamide treatment in an orthotopic mouse model. Elevated levels of androgen receptor full length and AR-V7 are key mechanisms underlying resistance to enzalutamide in PCa. Our findings showed that Gal-1 knockdown suppressed AR and AR-V7 expression and their transcriptional activity. In addition, pharmacological targeting of Gal-1 using LLS30 significantly suppressed the growth of enzalutamide-resistant PCa cells and exhibited synergistic effects when combined with enzalutamide. Notably, this combination significantly inhibited the growth of enzalutamide-resistant xenografts in vivo. Furthermore, RNA-seq analysis further revealed that LLS30 modulates AR and AR-V7 signaling through the inhibition of associated target genes. These findings highlighted Gal-1 as a promising therapeutic target for combating enzalutamide resistance in PCa. 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