دورية أكاديمية
أعرض في EDS

Neurokinin-1 receptor antagonist aprepitant regulates autophagy and apoptosis via ROS/JNK in intrahepatic cholangiocarcinoma.

التفاصيل البيبلوغرافية
العنوان: Neurokinin-1 receptor antagonist aprepitant regulates autophagy and apoptosis via ROS/JNK in intrahepatic cholangiocarcinoma.
المؤلفون: Yang Y; Institute of Digestive Endoscopy and Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China., Cao X; Institute of Digestive Endoscopy and Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China., Wang Y; Institute of Digestive Endoscopy and Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China., Wu X; Institute of Digestive Endoscopy and Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China., Zhou P; Lab Center, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China., Miao L; Institute of Digestive Endoscopy and Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China., Deng X; Institute of Digestive Endoscopy and Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
المصدر: Liver international : official journal of the International Association for the Study of the Liver [Liver Int] 2024 Jul; Vol. 44 (7), pp. 1651-1667. Date of Electronic Publication: 2024 Mar 30.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 101160857 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1478-3231 (Electronic) Linking ISSN: 14783223 NLM ISO Abbreviation: Liver Int Subsets: MEDLINE
أسماء مطبوعة: Publication: Malden, MA : Wiley-Blackwell
Original Publication: Oxford, UK : Blackwell Munksgaard, c2003-
مواضيع طبية MeSH: Aprepitant*/pharmacology , Aprepitant*/therapeutic use , Autophagy*/drug effects , Apoptosis*/drug effects , Cholangiocarcinoma*/drug therapy , Cholangiocarcinoma*/pathology , Cholangiocarcinoma*/metabolism , Reactive Oxygen Species*/metabolism , Mice, Nude* , Mice, Inbred BALB C* , Bile Duct Neoplasms*/drug therapy , Bile Duct Neoplasms*/pathology , Bile Duct Neoplasms*/metabolism , Xenograft Model Antitumor Assays* , Neurokinin-1 Receptor Antagonists*/pharmacology, Animals ; Humans ; Cell Line, Tumor ; Mice ; Male ; Female ; Receptors, Neurokinin-1/metabolism ; Middle Aged ; Cell Proliferation/drug effects
مستخلص: Background: Intrahepatic cholangiocarcinoma (iCCA) has a poor prognosis and limited treatment options. Aprepitant, a selective NK-1R antagonist, can inhibit the growth of various tumours in vitro and in vivo. However, it remains unclear whether aprepitant has cytotoxic effects on iCCA.
Methods: We measured the expression of SP/NK-1R 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-9810 and RBE cell lines to explore the effects of aprepitant in vivo. To elucidate the potential mechanisms, we explored the pro-apoptotic effect of aprepitant by flow cytometric, western blotting, ROS detection and JC-1 staining. Furthermore, we detected the autophagic level of HCCC-9810 and RBE by western blotting, mRFP-eGFP-LC3 adenovirus transfection and electron microscope.
Results: SP/NK-1R is significantly expressed in iCCA. Aprepitant inhibited human iCCA xenograft growth and dose-dependently decreased the viability of RBE and HCCC-9810 cells. Aprepitant-induced mitochondria-dependent apoptosis through ROS/JNK pathway. Additionally, pretreatment with z-VAD-fmk partly reversed the effect of aprepitant on cell viability, while NAC completely attenuated the cytotoxic effects of aprepitant in vitro. Furthermore, we observed the dynamic changes of autophagosome in RBE and HCCC-9810 cells treated with aprepitant.
Conclusion: SP/NK-1R 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.
(© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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معلومات مُعتمدة: Science and Technology Development Fund of Nanjing Medical University; National Natural Science Foundation of China
فهرسة مساهمة: Keywords: apoptosis; aprepitant; autophagy; intrahepatic cholangiocarcinoma
المشرفين على المادة: 1NF15YR6UY (Aprepitant)
0 (Reactive Oxygen Species)
0 (Neurokinin-1 Receptor Antagonists)
0 (Receptors, Neurokinin-1)
تواريخ الأحداث: Date Created: 20240330 Date Completed: 20240618 Latest Revision: 20240703
رمز التحديث: 20240703
DOI: 10.1111/liv.15904
PMID: 38554043
قاعدة البيانات: MEDLINE
الوصف
تدمد:1478-3231
DOI:10.1111/liv.15904