You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology III1 Apr 2017MP73-01 IMMUNE CHECKPOINT INHIBITOR COMBINED WITH THE GROWTH INHIBITOR LYCORINE SYNERGISTICALLY FUNCTION TO MEDIATE ANTI-TUMOR EFFECTS IN A MOUSE MODEL OF RENAL CELL CARCINOMA Xiezhao Li, Naijin Xu, Aibai Xu, Masami Watanabe, Peng Huang, Yasutomo Nasu, and Chunxiao Liu Xiezhao LiXiezhao Li More articles by this author , Naijin XuNaijin Xu More articles by this author , Aibai XuAibai Xu More articles by this author , Masami WatanabeMasami Watanabe More articles by this author , Peng HuangPeng Huang More articles by this author , Yasutomo NasuYasutomo Nasu More articles by this author , and Chunxiao LiuChunxiao Liu More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.3346AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Immune checkpoint inhibitors-based therapy is rapidly developing into an effective treatment option for a surprising range of cancers. Despite the autoimmune or inflammatory immune-mediated adverse effects which have been seen, the responses and overall survival benefits exhibited thus far warrant further clinical development. Lycorine, an alkaloid extracted from plants in the Amaryllidaceae family, which showed a strong anticancer effect by inducing cell lysis of various carcinomas. This study investigated the effectiveness of a combination therapy of lycorine and anti-CTLA-4 in a mouse model of renal cell carcinoma (RCC). METHODS We investigated the anti-tumor efficacy of lycorine in various RCC cell lines including Caki-1, ACHN, KPK-1 and Renca through XTT proliferation, scratch motility, migration and invasion assays. We also discuss that mechanism underlying this anticancer potential with flow cytometry and western blot. Furthermore, luciferase-expressing Renca cells were implanted in the left kidney and the lung of BALB/c mice to develop a RCC metastatic mouse model for investigated the combination therapy effect of lycorine and anti-CTLA-4. RESULTS We confirmed the anticancer potential of lycorine in vitro as observed time-dependent inhibition in several RCC cell lines. Moreover, lycorine suppressed the migratory and invasive abilities of Renca cells. The possible mechanism underlying this anticancer potential was cell cycle profile arrest. Lycorine and anti-CTLA-4 additively decreased tumor weight, lung metastasis, and luciferin-stained tumor images. Importantly, these effects were dependent on significantly suppressing regulatory T-cells while upregulating effector T-cells. CONCLUSIONS Herein, as we know, it's the first report that lycorine in combination with anti-CTLA-4 inhibited orthotopic and metastatic tumors by downregulating Treg, which was accompanied with upregulation of effector T-cells. Our findings suggest and indicate lycorine as a potent candidate for treating RCC and will serve as an excellent aid for developing a better treatment strategy for the use of immune checkpoint inhibitors in RCC. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e963 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Xiezhao Li More articles by this author Naijin Xu More articles by this author Aibai Xu More articles by this author Masami Watanabe More articles by this author Peng Huang More articles by this author Yasutomo Nasu More articles by this author Chunxiao Liu More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...