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Thymoquinone Augments Cisplatin-Induced Apoptosis on Esophageal Carcinoma Through Mitigating the Activation of JAK2/STAT3 Pathway

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Abstract

Background

Thymoquinone (TQ) is the major constituent of Nigella sativa seed and has shown biological activity in various human carcinomas. However, few studies have reported its effect on esophageal carcinoma (EC).

Aims

To explore the chemosensitive effect and mechanism of TQ in augmentation of cisplatin (DDP)-induced apoptosis of EC, both in vitro and in vivo.

Methods

The viability and apoptosis of esophageal carcinoma cells were detected by the Cell Counting Kit-8 assay, flow cytometry, and Hoechst 33258 staining. The expression levels of JAK2, p-JAK2, STAT3, p-STAT3, Bax, Bcl-2, Cyclin D1, Survivin, and caspase-3, 7, 9 were evaluated by western blot analysis. The histological changes were examined by TUNEL technique and immunohistochemical analysis.

Results

TQ enhanced the proapoptotic effect of DDP in human esophageal carcinoma cell line Eca-109, while blocking the activation of JAK2/STAT3 signaling pathway. The apoptosis of esophageal carcinoma cells was induced via blocking the activation of JAK2/STAT3 by using a molecular inhibitor (WP1066). Consistent with the in vivo and in vitro results, TQ increased cellular apoptosis and enriched the chemosensitivity of DDP.

Conclusions

TQ along with DDP may regulate the progression of EC and has potential to be a chemotherapeutic agent in EC.

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Acknowledgments

This study was supported by Grants from the National Natural Science Foundation from China (nos. 81372551, 81572426) and Natural Science Foundation Grant of Hubei Province (No. 2015CKB755).

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Authors and Affiliations

  1. Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 99 Zhang Zhi-dong Road, Wuhan, 430060, Hubei Province, People’s Republic of China

    Xue Hu, Jingjing Ma, Vikash Vikash, Jiao Li, Dandan Wu, Ya Liu, Jixiang Zhang & Weiguo Dong

  2. Key Laboratory of Hubei Province for Digestive System Disease, Wuhan, Hubei Province, People’s Republic of China

    Xue Hu

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  1. Xue Hu
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  2. Jingjing Ma
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Contributions

Author’s contribution

XH, JM and WD designed the research; XH, JL, DW, and YL performed the research; XH and JZ analyzed data; XH and VV wrote the paper.

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Correspondence to Weiguo Dong.

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Hu, X., Ma, J., Vikash, V. et al. Thymoquinone Augments Cisplatin-Induced Apoptosis on Esophageal Carcinoma Through Mitigating the Activation of JAK2/STAT3 Pathway. Dig Dis Sci 63, 126–134 (2018). https://doi.org/10.1007/s10620-017-4856-8

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  • DOI: https://doi.org/10.1007/s10620-017-4856-8

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