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已发表论文
补益舒郁丸通过 JAK2/STAT3 通路减少髓源性抑制细胞（MDSCs）的数量从而抑制三阴性乳腺癌前转移灶的形成
Authors Huang Y, Meng Y, Lou X, Feng D , Ling X, Jin Y, Lin X, Xie S
Received 25 June 2025
Accepted for publication 26 November 2025
Published 11 December 2025 Volume 2025:17 Pages 1213—1229
DOI https://doi.org/10.2147/BCTT.S549554
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Professor Harikrishna Nakshatri
Yazhen Huang,1,2,* YanYun Meng,1,* XiaoShan Lou,1,3 Doudou Feng,1 XiangLi Ling,1 Yang Jin,4 Xiangping Lin,5 Su Xie1,6
1Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, Guizhou, 550004, People’s Republic of China; 2Chengdu Hospital of Integrated Traditional and Western Medicine, Chengdu, Sichuan, 610095, People’s Republic of China; 3Teaching and Research Section of Acupuncture and Moxibustion, Zunyi Medical College, Zunyi, Guizhou, 563006, People’s Republic of China; 4Guizhou Medical University, Guiyang, Guizhou, 550004, People’s Republic of China; 5Department of Pharmacy, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, People’s Republic of China; 6Department of Traditional Chinese Medicine, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Su Xie, Department of Traditional Chinese Medicine, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, People’s Republic of China, Tel +86 0851 86773643, Email xiesutcm@163.com Xiangping Lin, Department of Pharmacy, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, People’s Republic of China, Tel +86 0851 86774148, Email linxiangping@gmc.edu.cn
Purpose: To investigate the effect of modified Shuyu pill on the timing of TNBC metastasis, MDSCs recruitment in tumor tissues and distant target organs, and the impact on the JAK2/STAT3 signaling pathway.
Methods: The fingerprint profile of the modified Shuyu pill was obtained using UPLC-Q-Exactive HRMS technology. A TNBC-bearing mouse model was established, and the mice were treated with modified Shuyu pill granules (low, medium, and high doses), paclitaxel (PTX), or saline for 25 days. Tumor growth was monitored during treatment, and small animal in vivo imaging was performed on days 1, 7, 14, 21, and 25. On day 21 of treatment, flow cytometry was used to assess the proportion of G-MDSCs and M-MDSCs in peripheral blood, spleen, lungs, and tumor tissues. Immunofluorescence was used to detect the number and distribution of MDSCs in the lungs and liver. Western blotting and RT-qPCR were used to detect the expression of proteins and genes related to the JAK2/STAT3 signaling pathway in tumor tissues.
Results: The modified Shuyu pill inhibited tumor growth and distant metastasis in 4T1 tumor-bearing mice, and its anti-tumor effect was enhanced when combined with paclitaxel. More importantly, modified Shuyu pill suppressed the recruitment of MDSCs in the peripheral blood, spleen, lungs, liver, and tumors of tumor-bearing mice, thereby inhibiting the formation of the pre-metastatic niche. Mechanistically, modified Shuyu pill inhibited the expression of proteins in the JAK2/STAT3 signaling pathway, including IL-6, JAK2, p-JAK2, STAT3, p-STAT3 (Tyr705), p-STAT3 (Ser727), S100A8, S100A9, NF-κB, MMP2, and MMP9, and this effect was more pronounced when combined with paclitaxel.
Conclusion: The modified Shuyu Pill can downregulate the JAK2/STAT3 signaling pathway, reduce the number of MDSCs in the tumor microenvironment and distant lung tissues of tumor-bearing mice, inhibit the formation of pre-metastatic niches, and ultimately suppress tumor growth and metastasis.
Keywords: modified Shuyu pill, triple-negative breast cancer, MDSCs, pre-metastatic ecological niches, JAK2/STAT3 signaling pathway
1Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, Guizhou, 550004, People’s Republic of China; 2Chengdu Hospital of Integrated Traditional and Western Medicine, Chengdu, Sichuan, 610095, People’s Republic of China; 3Teaching and Research Section of Acupuncture and Moxibustion, Zunyi Medical College, Zunyi, Guizhou, 563006, People’s Republic of China; 4Guizhou Medical University, Guiyang, Guizhou, 550004, People’s Republic of China; 5Department of Pharmacy, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, People’s Republic of China; 6Department of Traditional Chinese Medicine, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Su Xie, Department of Traditional Chinese Medicine, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, People’s Republic of China, Tel +86 0851 86773643, Email xiesutcm@163.com Xiangping Lin, Department of Pharmacy, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, People’s Republic of China, Tel +86 0851 86774148, Email linxiangping@gmc.edu.cn
Purpose: To investigate the effect of modified Shuyu pill on the timing of TNBC metastasis, MDSCs recruitment in tumor tissues and distant target organs, and the impact on the JAK2/STAT3 signaling pathway.
Methods: The fingerprint profile of the modified Shuyu pill was obtained using UPLC-Q-Exactive HRMS technology. A TNBC-bearing mouse model was established, and the mice were treated with modified Shuyu pill granules (low, medium, and high doses), paclitaxel (PTX), or saline for 25 days. Tumor growth was monitored during treatment, and small animal in vivo imaging was performed on days 1, 7, 14, 21, and 25. On day 21 of treatment, flow cytometry was used to assess the proportion of G-MDSCs and M-MDSCs in peripheral blood, spleen, lungs, and tumor tissues. Immunofluorescence was used to detect the number and distribution of MDSCs in the lungs and liver. Western blotting and RT-qPCR were used to detect the expression of proteins and genes related to the JAK2/STAT3 signaling pathway in tumor tissues.
Results: The modified Shuyu pill inhibited tumor growth and distant metastasis in 4T1 tumor-bearing mice, and its anti-tumor effect was enhanced when combined with paclitaxel. More importantly, modified Shuyu pill suppressed the recruitment of MDSCs in the peripheral blood, spleen, lungs, liver, and tumors of tumor-bearing mice, thereby inhibiting the formation of the pre-metastatic niche. Mechanistically, modified Shuyu pill inhibited the expression of proteins in the JAK2/STAT3 signaling pathway, including IL-6, JAK2, p-JAK2, STAT3, p-STAT3 (Tyr705), p-STAT3 (Ser727), S100A8, S100A9, NF-κB, MMP2, and MMP9, and this effect was more pronounced when combined with paclitaxel.
Conclusion: The modified Shuyu Pill can downregulate the JAK2/STAT3 signaling pathway, reduce the number of MDSCs in the tumor microenvironment and distant lung tissues of tumor-bearing mice, inhibit the formation of pre-metastatic niches, and ultimately suppress tumor growth and metastasis.
Keywords: modified Shuyu pill, triple-negative breast cancer, MDSCs, pre-metastatic ecological niches, JAK2/STAT3 signaling pathway