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Suppression of JAK2/STAT3 Pathway by Notoginsenoside R1 Reduces Epithelial-Mesenchymal Transition in Non-small Cell Lung Cancer

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Abstract

It has bene reported that a novel saponin-notoginsenoside R1 (NGR1) possesses strong anti-tumor activities. This study aimed to investigate the role and mechanism of NGR1 in non-small cell lung cancer (NSCLC). NSCLC cell viability, proliferation, migration, and invasiveness were assessed using the ex vivo assays. NSCLC xenograft mouse models were constructed to confirm the role of NGR1 in vivo. Epithelial-mesenchymal transition (EMT)-related proteins and key markers in the JAK2/STAT3 pathway were examined using immunoblotting and immunohistochemistry analyses. NGR1 treatment suppressed NSCLC cell growth ex vivo and in vivo. It also decreased the migratory and invasive capacities of NSCLC cells. Additionally, NGR1 increased E-cadherin expression and reduced N-cadherin, vimentin, and snail expression in TGF-β1-treated NSCLC cells and xenograft tumors. JAK2/STAT3 pathway was inhibited by NGR1. Moreover, a specific inhibitor of JAK2, AG490, or STAT3 silencing significantly enhanced the effects of NGR1 against the EMT process in NSCLC cells. NGR1 restrains EMT process in NSCLC by inactivating JAK2/STAT3 signaling, suggesting the potential of NGR1 in anti-NSCLC therapy.

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Data Availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Medical Laboratory, Wuhan Hospital of Traditional Chinese Medicine, Wuhan, 430014, China

    Min Wan & Hong Yu

  2. Department of Oncology Hematology, Qianjiang Central Hospital, No.22 Zhanghua Road, Qianjiang, 433100, Hubei, China

    Haoqing Zhai

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Contributions

Min Wan conceived and designed the experiments. Min Wan, Hong Yu and Haoqing Zhai carried out the experiments. Min Wan and Haoqing Zhai analyzed the data. Min Wan and Haoqing Zhai drafted the manuscript. All authors agreed to be accountable for all aspects of the work. All authors have read and approved the final manuscript.

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Correspondence to Haoqing Zhai.

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Animal experiments were approved by the Animal Ethics Committee of Wuhan Myhalic Biotechnology Co., Ltd (No.HLK-202209016, Date: 2022.9.6) and performed under the requirements of the Laboratory Animal Act of the People’s Republic of China.

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Wan, M., Yu, H. & Zhai, H. Suppression of JAK2/STAT3 Pathway by Notoginsenoside R1 Reduces Epithelial-Mesenchymal Transition in Non-small Cell Lung Cancer. Mol Biotechnol (2024). https://doi.org/10.1007/s12033-024-01136-3

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