Pd51-11 Icarside Ii and Sunitinib Cooperatively Induce Apoptosis of Renal Cell Carcinoma Cells via Activating the Atf4/Noxa Axis and Inhibiting the Pi3k/Akt Pathway

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology II (PD51)1 May 2024PD51-11 ICARSIDE II AND SUNITINIB COOPERATIVELY INDUCE APOPTOSIS OF RENAL CELL CARCINOMA CELLS VIA ACTIVATING THE ATF4/NOXA AXIS AND INHIBITING THE PI3K/AKT PATHWAY Yu Ren, Xue Wang, Jie Yao, and Rui Yu Yu RenYu Ren , Xue WangXue Wang , Jie YaoJie Yao , and Rui YuRui Yu View All Author Informationhttps://doi.org/10.1097/01.JU.0001009360.84490.42.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Renal cell carcinoma (RCC) is a common yet lethal urological malignancy and distant metastasis, leading to a poor prognosis. Sunitinib is a tyrosine kinase inhibitor that can be potentially used to treat RCC. However, the drug resistance for sunitinib often limits its applications., warranting the need to identify strategies that can improve its efficacy. Icariside II (ICS II), an active flavonoid, has been used in traditional Chinese medicine. In this study, we evaluated the combined effects of sunitinib and ICS II on RCC. METHODS: The MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to measure cell viability. Colony formation assay was used to evaluate cell proliferation ability as well. Cellular apoptosis was detected by flow cytometry analysis. Changes in the mRNA and protein levels of various genes were measured by quantitative real-time PCR (qRT-PCR) and western blotting, respectively. RNA interference technology (RNAi) was used to knock down multiple genes. RESULTS: Our results showed synergistic inhibition of RCC cell proliferation by combining ICS II and sunitinib. ICS II and sunitinib also cooperatively induced apoptosis in a caspase- dependent manner in RCC cells. The underlying mechanisms fueling these events involve ICS II- and sunitinib-mediated downregulation of B-cell lymphoma-extra-large (Bcl-xl) and upregulation of Noxa in RCC cells. Co-treatment of ICS II and sunitinib induced endoplasmic reticulum (ER) stress and activated the Activating transcription factor 4 (ATF4)/Noxa axis in RCC cells. Moreover, ICS II and sunitinib combination treatment inhibited the Phosphoinositide 3-kinase (PI3K)/Akt signaling pathway in RCC cells. CONCLUSIONS: Our data collectively suggested that combination therapy of ICS II and sunitinib might be a potential treatment strategy for RCC. Download PPTDownload PPTDownload PPTDownload PPTDownload PPT Source of Funding: This project is supported by the Science and Technology Program of Traditional Chinese Medicine in Zhejiang Province © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1069 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Yu Ren More articles by this author Xue Wang More articles by this author Jie Yao More articles by this author Rui Yu More articles by this author Expand All Advertisement PDF downloadLoading ...