{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T21:40:03Z","timestamp":1788903603900,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,3,30]],"date-time":"2024-03-30T00:00:00Z","timestamp":1711756800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Intrahepatic cholangiocarcinoma (iCCA) has a poor prognosis and limited treatment options. Aprepitant, a selective NK\u20101R antagonist, can inhibit the growth of various tumours in\u00a0vitro and in\u00a0vivo. However, it remains unclear whether aprepitant has cytotoxic effects on iCCA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We measured the expression of SP\/NK\u20101R in clinical samples of iCCA by immunohistochemistry. Then, we detected the cytotoxic effects of aprepitant on iCCA cells via MTT, EdU and colony formation assay. We constructed a subcutaneous xenograft model of BALB\/c nude mice by using HCCC\u20109810 and RBE cell lines to explore the effects of aprepitant in\u00a0vivo. To elucidate the potential mechanisms, we explored the pro\u2010apoptotic effect of aprepitant by flow cytometric, western blotting, ROS detection and JC\u20101 staining. Furthermore, we detected the autophagic level of HCCC\u20109810 and RBE by western blotting, mRFP\u2010eGFP\u2010LC3 adenovirus transfection and electron microscope.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SP\/NK\u20101R is significantly expressed in iCCA. Aprepitant inhibited human iCCA xenograft growth and dose\u2010dependently decreased the viability of RBE and HCCC\u20109810 cells. Aprepitant\u2010induced mitochondria\u2010dependent apoptosis through ROS\/JNK pathway. Additionally, pretreatment with z\u2010VAD\u2010fmk partly reversed the effect of aprepitant on cell viability, while NAC completely attenuated the cytotoxic effects of aprepitant in\u00a0vitro. Furthermore, we observed the dynamic changes of autophagosome in RBE and HCCC\u20109810 cells treated with aprepitant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>SP\/NK\u20101R signalling is significantly activated in iCCA and promotes the proliferation of iCCA cells. By contrast, aprepitant can induce autophagy and apoptosis in iCCA cells via ROS accumulation and subsequent activation of JNK.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15904","type":"journal-article","created":{"date-parts":[[2024,3,30]],"date-time":"2024-03-30T11:10:09Z","timestamp":1711797009000},"page":"1651-1667","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Neurokinin\u20101 receptor antagonist aprepitant regulates autophagy and apoptosis via <scp>ROS<\/scp>\/<scp>JNK<\/scp> in intrahepatic cholangiocarcinoma"],"prefix":"10.1111","volume":"44","author":[{"given":"Yang","family":"Yang","sequence":"first","affiliation":[{"name":"Institute of Digestive Endoscopy and Medical Center for Digestive Diseases Second Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu 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