Cinobufagin exerts an antitumor effect in non-small-cell lung cancer by blocking STAT3 signaling

Yan, Sunshun; Ma, Chunbo; Zhou, Feng; Zheng, Hailun; Yang, Lehe; Xiao, Zhongxiang; Zhu, Jiandong; Zhao, Haiyang; Zhao, Chengguang; Xu, Xiaoling

doi:10.7150/jca.86544

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J Cancer 2023; 14(17):3309-3320. doi:10.7150/jca.86544 This issue Cite

Research Paper

Cinobufagin exerts an antitumor effect in non-small-cell lung cancer by blocking STAT3 signaling

Sunshun Yan^1,3,#, Chunbo Ma^3,4,5,#, Feng Zhou^4,5,#, Hailun Zheng³, Lehe Yang⁵, Zhongxiang Xiao⁵, Jiandong Zhu⁵, Haiyang Zhao^4,✉, Chengguang Zhao^5,✉, Xiaoling Xu^1,2,✉

1. Cheeloo College of Medicine, Shandong University, 44 Cultural West Road, Shandong Province 250012, China.
2. The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China.
3. The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.
4. The Institute of Life Sciences, Wenzhou University, Wenzhou, Zhejiang 325035, China.
5. Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325600, China.
#These authors have contributed equally to this work.

✉ Corresponding authors: Xiaoling Xu, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China. Email: xxlahh08com. Chengguang Zhao Ph.D., School of P More

Citation:

Yan S, Ma C, Zhou F, Zheng H, Yang L, Xiao Z, Zhu J, Zhao H, Zhao C, Xu X. Cinobufagin exerts an antitumor effect in non-small-cell lung cancer by blocking STAT3 signaling. J Cancer 2023; 14(17):3309-3320. doi:10.7150/jca.86544. https://www.jcancer.org/v14p3309.htm

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Abstract

Background: Non-small-cell lung cancer (NSCLC) is the most common histological subtype of lung cancer with significant morbidity and mortality rates worldwide. Cinobufagin, the primary component of Chansu and the major active ingredient of cinobufacini, has attracted widespread attention for its excellent anticancer effects, but its activity remains poorly characterized in NSCLC.

Methods: The functions of cinobufagin treatment in anti-tumor was evaluated using various in vitro and in vivo assays. The change of STAT3 signaling by cinobufagin was analyzed using molecular docking, immunofluorescence technic and western blotting.

Results: In vitro, we confirmed the inhibitory effect of cinobufagin on cell viability, proliferation, migration, epithelial-mesenchymal transition (EMT), as well as an apoptosis-inducing effect. The antitumor effects of cinobufagin were confirmed in vivo by measuring tumor growth in a mouse xenograft model. Cinobufagin was found to significantly inhibit the phosphorylation of signal transducer and activator of transcription 3 (STAT3) at tyrosine 705 (Y705) in a time- and concentration-dependent manner. Moreover, cinobufagin reversed IL-6-induced nuclear translocation of STAT3.

Conclusions: Our study has demonstrated that cinobufagin exerts an antitumor effect in non-small-cell lung cancer by blocking STAT3 signaling, and cinobufagin is a promising candidate agent for NSCLC therapy.

Keywords: Non-small-cell lung cancer, Cinobufagin, STAT3

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APA

Yan, S., Ma, C., Zhou, F., Zheng, H., Yang, L., Xiao, Z., Zhu, J., Zhao, H., Zhao, C., Xu, X. (2023). Cinobufagin exerts an antitumor effect in non-small-cell lung cancer by blocking STAT3 signaling. Journal of Cancer, 14(17), 3309-3320. https://doi.org/10.7150/jca.86544.

ACS

Yan, S.; Ma, C.; Zhou, F.; Zheng, H.; Yang, L.; Xiao, Z.; Zhu, J.; Zhao, H.; Zhao, C.; Xu, X. Cinobufagin exerts an antitumor effect in non-small-cell lung cancer by blocking STAT3 signaling. J. Cancer 2023, 14 (17), 3309-3320. DOI: 10.7150/jca.86544.

NLM

CSE

Yan S, Ma C, Zhou F, Zheng H, Yang L, Xiao Z, Zhu J, Zhao H, Zhao C, Xu X. 2023. Cinobufagin exerts an antitumor effect in non-small-cell lung cancer by blocking STAT3 signaling. J Cancer. 14(17):3309-3320.

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