American Association for Cancer Research
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10780432ccr143382-sup-143184_2_figure_3109363_ntc69n.png (2.01 MB)

Figure S2 from IL1 Receptor Antagonist Inhibits Pancreatic Cancer Growth by Abrogating NF-κB Activation

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posted on 2023-03-31, 18:47 authored by Zhuonan Zhuang, Huai-Qiang Ju, Mitzi Aguilar, Takashi Gocho, Hao Li, Tomonori Iida, Harold Lee, Xiaoqiang Fan, Haijun Zhou, Jianhua Ling, Zhongkui Li, Jie Fu, Min Wu, Min Li, Davide Melisi, Yoichiro Iwakura, Kesen Xu, Jason B. Fleming, Paul J. Chiao

Figure S2. A, Western blot analysis to determine the phosphorylation of P65 in AsPc1 cells pretreated with 50 μM NAC (a ROS scavenger) for 1 hour followed by treatment with gemcitabine (Gem, 10μM).

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ARTICLE ABSTRACT

Purpose: Constitutive NF-κB activation is identified in about 70% of pancreatic ductal adenocarcinoma (PDAC) cases and is required for oncogenic KRAS-induced PDAC development in mouse models. We sought to determine whether targeting IL-1α pathway would inhibit NF-κB activity and thus suppress PDAC cell growth.Experimental Design: We determined whether anakinra, a human IL-1 receptor (rhIL-1R) antagonist, inhibited NF-κB activation. Assays for cell proliferation, migration, and invasion were performed with rhIL-1R antagonist using the human PDAC cell lines AsPc1, Colo357, MiaPaCa-2, and HPNE/K-rasG12V/p16sh. In vivo NF-κB activation–dependent tumorigenesis was assayed using an orthotopic nude mouse model (n = 20, 5 per group) treated with a combination of gemcitabine and rhIL-1RA.Results: rhIL-1R antagonist treatment led to a significant decrease in NF-κB activity. PDAC cells treated with rhIL-1R antagonist plus gemcitabine reduced proliferation, migration, and invasion as compared with single gemcitabine treatment. In nude mice, rhIL-1R antagonist plus gemcitabine significantly reduced the tumor burden (gemcitabine plus rhIL-1RA vs. control, P = 0.014).Conclusions: We found that anakinra, an FDA-approved drug that inhibits IL-1 receptor (IL-1R), when given with or without gemcitabine, can reduce tumor growth by inhibiting IL1α-induced NF-κB activity; this result suggests that it is a useful therapeutic approach for PDAC. Clin Cancer Res; 22(6); 1432–44. ©2015 AACR.

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