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Inflammation Research

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26.06.2019 | Original Research Paper

Inhibition of JAK2/STAT3 signaling pathway protects mice from the DDP-induced acute kidney injury in lung cancer

verfasst von: Lei Zhang, Peng Lu, Xu Guo, Ting Liu, Xu Luo, Yi-Tang Zhu

Erschienen in: Inflammation Research | Ausgabe 9/2019

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Abstract

Objective

To explore AG490 (the inhibitor of Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3 pathway) in cisplatin (DDP)-induced acute kidney injury (AKI) in mice with lung cancer.

Methods

Mice were randomly divided into normal, model, AG490, DDP and DDP + AG490 groups. The lung cancer models were established except for Normal group. The levels of blood urea nitrogen (BUN) and creatinine and the status of oxidative stress were detected. Then, histological changes were assessed by HE and PAS staining and apoptosis by TUNEL experiment. The molecule expressions were detected by qRT-PCR and western blot, and immunohistochemistry, respectively.

Results

DDP inhibited the tumor growth in mice with lung cancer, which was further promoted by the combination with AG490. Mice in the DDP group had elevated levels of BUN and creatinine than those in the Normal group with the increased inflammatory cytokines (TNF-α, IL-6, MCP-1 and CXCL-1) and malondialdehyde (MDA) level and the decreased glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). In addition, DDP could activate the JAK2/STAT3 pathway to promote the apoptosis by upregulating Bax, cleaved caspase-9 and cleaved caspase-3 while downregulating the Bcl-2 in the kidney tissues. DDP + AG490 group showed the alleviated AKI and the improvements in oxidative stress, inflammatory responses and apoptosis in the kidney tissues, as compared to DDP group.

Conclusion

AG490 alleviated DDP-induced AKI in lung cancer mice with improved oxidative stress and inflammation, and the suppression of JAK2/STAT3 pathway.

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Titel: Inhibition of JAK2/STAT3 signaling pathway protects mice from the DDP-induced acute kidney injury in lung cancer
verfasst von: Lei Zhang
Peng Lu
Xu Guo
Ting Liu
Xu Luo
Yi-Tang Zhu
Publikationsdatum: 26.06.2019
Verlag: Springer International Publishing
Erschienen in: Inflammation Research / Ausgabe 9/2019
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-019-01258-4

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Inhibition of JAK2/STAT3 signaling pathway protects mice from the DDP-induced acute kidney injury in lung cancer

Abstract

Objective

Methods

Results

Conclusion

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Abstract

Objective

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