{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T05:49:23Z","timestamp":1776923363961,"version":"3.51.2"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T00:00:00Z","timestamp":1768089600000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Prostate Cancer"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Most therapy options for castration\u2010resistant prostate cancer (CRPCa) target the androgen axis. Human kallikrein\u2013related peptidase (KLK) 2, a serine protease, is a downstream target gene of the androgen receptor (AR) involved in cancer progression, but also known to have an AR\u2010independent function. Tissue KLKs, especially KLK2, are promising targets for therapy in advanced PCa because of their high PCa specificity and their correlation to the rising cancer grade and stage. By inhibition with the recombinant protease inhibitor MDPK67b targeting KLK2 and other trypsin\u2010like KLKs including KLK4 and KLK14, we investigated the antitumor response and the influence on AR downstream target genes with MDPK67b in PCa cell lines in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Human PCa cells were cultured in a charcoal\u2010stripped media and treated with MDPK67b (0.75\u2009mg\/mL). Cell viability was measured by CellTiter\u2010Glo luminescent assay, cell death by flow cytometry. Gene analysis of AR, PSA, and PSMA was performed by qPCR. Correlating protein levels were evaluated by immunoblotting and confirmed by immunocytochemical staining.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Treatment with 0.75\u2009mg\/mL MDPK67b led to a reduction of cell proliferation of 40% by day 5 in androgen\u2010sensitive LNCaP cells. Immunostaining confirmed the decrease in cell proliferation by antibody labeling of Ki\u201067. Treatment induced apoptosis, which was visible by flow cytometry of annexin V in LNCaP cells. Further, MDPK67b induced a reduction in AR and PSA gene and protein expression but upregulated PSMA, a target for PCa imaging and therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Treatment with MDPK67b demonstrates a significant antitumor effect by relevant reduction in cell proliferation and upregulation of apoptosis in LNCaP cells. Blockage of secreted KLKs can downregulate the AR and thereby influence its downstream target genes like PSA and PSMA. Upregulation of PSMA can lead to a theranostic, that is, therapeutic and diagnostic, advantage in clinics in a CR setting. Therefore, inhibition of KLKs represents a promising and AR\u2010independent approach to treat advanced and CRPCa.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov ID:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04644770\">NCT04644770<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/proc\/7871208","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T05:03:47Z","timestamp":1768194227000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Inhibition of Growth and Induction of Apoptosis of Human Prostate Cancer Cells by Enzymatic Blockage of 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