Research Papers:

Pantoprazole blocks the JAK2/STAT3 pathway to alleviate skeletal muscle wasting in cancer cachexia by inhibiting inflammatory response

Dunwei Guo, Chaoyi Wang, Qiang Wang, Zhongpeng Qiao and Hua Tang _

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Oncotarget. 2017; 8:39640-39648. https://doi.org/10.18632/oncotarget.17387

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Dunwei Guo1, Chaoyi Wang2, Qiang Wang3, Zhongpeng Qiao1 and Hua Tang1

1Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University Chongqing 400016, China

2Department of Breast Surgery, Chongqing Three Gorges Central Hospital, Chongqing 404000, China

3Department of Gastrointestinal Surgery, Suining Municipal Central Hospital, Suining, Sichuan 629000, China

Correspondence to:

Hua Tang, email: [email protected]

Keywords: cancer cachexia, JAK2/STAT3, ubiquitin, Fbx32, pantoprazole

Received: December 10, 2016     Accepted: March 27, 2017     Published: April 24, 2017


Objective: Cancer cachexia is often present in patients with advanced malignant tumors, and the subsequent body weight reduction results in poor quality of life. However, there has been no progress in developing effective clinical therapeutic strategies for skeletal muscle wasting in cancer cachexia. Herein, we explored the functions of pantoprazole on cancer cachexia skeletal muscle wasting.

Methods: The mouse colon adenocarcinoma cell line C26 was inoculated in the right forelimb of male BALB/C mice to establish a cancer cachexia model. The animals were treated with or without different concentrations of pantoprazole orally, and the body weight, tumor growth, spontaneous activity, and muscle functions were determined at various time points. Two weeks later, the levels of serum IL-6 and TNF-α, the mRNA levels of gastrocnemius JAK2 and STAT3, and the expression levels of p-JAK2, p-STAT3, Fbx32, and MuRF1 were examined with ELISA assay, qRT-PCR assay, and Western blotting, respectively. Further studies were performed to assess the levels of Fbx32 and MuRF1 expression and morphological changes.

Results: Pantoprazole can alleviate cancer cachexia-induced body weight reduction and inhibit skeletal muscle wasting in a dose-dependent manner. Our results indicated that pantoprazole treatment can decrease the levels of serum IL-6 and TNF-α (56.3% and 67.6%, respectively), and inhibit the activation of the JAK2/STAT3 signaling pathway. Moreover, the expression levels of MuRF1 and Fbx32 were also suppressed after pantoprazole treatment.

Conclusion: Our findings suggested that pantoprazole can alleviate cancer cachexia skeletal muscle wasting by inhibiting the inflammatory response and blocking the JAK2/STAT3 or ubiquitin proteasome pathway.

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