Breast cancer (Dove Medical Press) · 2025
The Modified Shuyu Pill Inhibits the Formation of Pre-Metastatic Niches in Triple-Negative Breast Cancer by Reducing the Number of Myeloid-Derived Suppressor Cells (MDSCs) via the JAK2/STAT3 Pathway.
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Huang Yazhen, Meng YanYun, Lou XiaoShan, Feng Doudou, Ling XiangLi, Jin Yang, Lin Xiangping, Xie Su
Аннотация
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.
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.