{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:01:30Z","timestamp":1787022090298,"version":"build-2736575974"},"reference-count":29,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T00:00:00Z","timestamp":1630540800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Nuclear factor kappa B (NF-\u03baB) is a transcriptional factor that can be activated by radiotherapy and chemotherapy. The synthetic protease inhibitor nafamostat mesilate (NM) inhibits NF-\u03baB activity and exerts antitumor actions in various types of cancer. In the present study, we hypothesized that NM might enhance the antitumor action of radiotherapy on gallbladder cancer (GBC) cells by inhibiting radiation-induced NF-\u03baB activity. Thus, we investigated the correlation between radiotherapy and NF-\u03baB activity in GBC cells. We assessed the\n                    <jats:italic>in vitro<\/jats:italic>\n                    effects of radiotherapy with or without NM on NF-\u03baB activity, apoptosis of GBC cells (NOZ and OCUG-1), induction of apoptotic cascade, cell cycle progression, and viability of GBC cells using four treatment groups: 1) radiation (5 Gy) alone; 2) NM (80 \u03bcg\/mL and 40 \u03bcg\/mL, respectively) alone; 3) combination (radiation and NM); and 4) vehicle (control). The same experiments were performed\n                    <jats:italic>in vivo<\/jats:italic>\n                    using a xenograft GBC mouse model.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , NM inhibited radiation-induced NF-\u03baB activity. Combination treatment significantly attenuated cell viability and increased cell apoptosis and G2\/M phase cell cycle arrest compared with those in the other groups for NOZ and OCUG-1 cells. Moreover, combination treatment upregulated the expression of apoptotic proteins compared with that after the other treatments.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , NM improved the antitumor action of radiation and increased the population of Ki-67-positive cells. Overall, NM enhanced the antitumor action of radiotherapy on GBC cells by suppressing radiation-induced NF-\u03baB activity. Thus, the combination of radiotherapy and NM may be useful for the treatment of locally advanced unresectable GBC.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0257019","type":"journal-article","created":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T13:41:20Z","timestamp":1630590080000},"page":"e0257019","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Nafamostat mesilate, a nuclear factor kappa B inhibitor, enhances the antitumor action of radiotherapy on gallbladder cancer 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