GuBenPeiYuan Formula Inhibits Lung Cancer Metastasis by Suppressing Myeloid-Derived Suppressor Cells and Related Immune Cells
Background: Lung cancer remains the leading cause of cancer-related morbidity and mortality all over the world, with high rates of locoregional recurrence and distant metastasis even after curative-intent surgical resection. The mechanisms of the tumor microenvironment’s role in supporting metastasi...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2025-04-01
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| Series: | Integrative Cancer Therapies |
| Online Access: | https://doi.org/10.1177/15347354251324650 |
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| author | Yizhao Du MD Yongming Zhou PhD Lijing Jiao PhD Wenxiao Yang PhD Ling Xu PhD Hailun Zhou MD Jingwen Zhao MD Quanyao Li MD Yang Han MD Yabin Gong PhD Qin Wang PhD |
| author_facet | Yizhao Du MD Yongming Zhou PhD Lijing Jiao PhD Wenxiao Yang PhD Ling Xu PhD Hailun Zhou MD Jingwen Zhao MD Quanyao Li MD Yang Han MD Yabin Gong PhD Qin Wang PhD |
| author_sort | Yizhao Du MD |
| collection | DOAJ |
| description | Background: Lung cancer remains the leading cause of cancer-related morbidity and mortality all over the world, with high rates of locoregional recurrence and distant metastasis even after curative-intent surgical resection. The mechanisms of the tumor microenvironment’s role in supporting metastasis through the formation of pre-metastatic niches are crucial areas of investigation. Methods: Lung metastasis models were established by injecting Lewis lung cancer cells (LLCs) into the tail vein of 20 specific pathogen free (SPF)—grade male C57BL/6 mice. The mice were divided into 4 groups: control (physiological saline), GuBenPeiYuan (GBPY) medium-dose (25 g/kg), GBPY high-dose (50 g/kg), all administered by gavage, and gemcitabine (50 mg/kg, administered by intraperitoneal injection on days 1, 4, 7, 10, and 13), the total treatment duration was 14 days. Qualitative and quantitative analyses of GBPY were performed using Ultra-Performance Liquid Chromatography (UPLC). Metastasis was observed using hematoxylin and eosin (H&E) staining, and the expression of immune cells was assessed by flow cytometry and immunofluorescence staining. Mechanistic insights were gained through Western blot. Results: The high-dose GBPY and gemcitabine groups showed significantly fewer lung metastatic tumors ( P = .002; P < .001), while no significant difference was observed between the medium-dose group and control group ( P = .438). Flow cytometry results indicated that high-dose GBPY significantly downregulated Myeloid-Derived Suppressor Cells (MDSCs) and G-MDSCs ( P = .002 and P = .001, respectively), upregulated dendritic cells (DCs; P = .021), increased M1 macrophages (F4/80 + /iNOS + ; P = .001) and decreased M2 macrophages (CD206 + F4/80 + ) ( P < .001). Furthermore, Western blot results showed that the high-dose GBPY group significantly inhibited the expression of p-JAK2, p-STAT3 ( P = .013, P = .001 respectively). Conclusions: The GBPY Formula may reduce lung cancer metastasis and recurrence by inhibiting the JAK2/STAT3 pathway, downregulating the presence of MDSCs, upregulating the proportion of DCs, and promoting the polarization of M2 macrophages to M1 macrophages. These changes enhance the anti-tumor immune response, contributing to the reduction of lung cancer metastasis and recurrence. |
| format | Article |
| id | doaj-art-598c68dddcd4411e8d5271f35239fd66 |
| institution | DOAJ |
| issn | 1552-695X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Integrative Cancer Therapies |
| spelling | doaj-art-598c68dddcd4411e8d5271f35239fd662025-08-20T03:14:01ZengSAGE PublishingIntegrative Cancer Therapies1552-695X2025-04-012410.1177/15347354251324650GuBenPeiYuan Formula Inhibits Lung Cancer Metastasis by Suppressing Myeloid-Derived Suppressor Cells and Related Immune CellsYizhao Du MD0Yongming Zhou PhD1Lijing Jiao PhD2Wenxiao Yang PhD3Ling Xu PhD4Hailun Zhou MD5Jingwen Zhao MD6Quanyao Li MD7Yang Han MD8Yabin Gong PhD9Qin Wang PhD10Yueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaYueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaYueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaYueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaYueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaYueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaYueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaYueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaYueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaYueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaYueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaBackground: Lung cancer remains the leading cause of cancer-related morbidity and mortality all over the world, with high rates of locoregional recurrence and distant metastasis even after curative-intent surgical resection. The mechanisms of the tumor microenvironment’s role in supporting metastasis through the formation of pre-metastatic niches are crucial areas of investigation. Methods: Lung metastasis models were established by injecting Lewis lung cancer cells (LLCs) into the tail vein of 20 specific pathogen free (SPF)—grade male C57BL/6 mice. The mice were divided into 4 groups: control (physiological saline), GuBenPeiYuan (GBPY) medium-dose (25 g/kg), GBPY high-dose (50 g/kg), all administered by gavage, and gemcitabine (50 mg/kg, administered by intraperitoneal injection on days 1, 4, 7, 10, and 13), the total treatment duration was 14 days. Qualitative and quantitative analyses of GBPY were performed using Ultra-Performance Liquid Chromatography (UPLC). Metastasis was observed using hematoxylin and eosin (H&E) staining, and the expression of immune cells was assessed by flow cytometry and immunofluorescence staining. Mechanistic insights were gained through Western blot. Results: The high-dose GBPY and gemcitabine groups showed significantly fewer lung metastatic tumors ( P = .002; P < .001), while no significant difference was observed between the medium-dose group and control group ( P = .438). Flow cytometry results indicated that high-dose GBPY significantly downregulated Myeloid-Derived Suppressor Cells (MDSCs) and G-MDSCs ( P = .002 and P = .001, respectively), upregulated dendritic cells (DCs; P = .021), increased M1 macrophages (F4/80 + /iNOS + ; P = .001) and decreased M2 macrophages (CD206 + F4/80 + ) ( P < .001). Furthermore, Western blot results showed that the high-dose GBPY group significantly inhibited the expression of p-JAK2, p-STAT3 ( P = .013, P = .001 respectively). Conclusions: The GBPY Formula may reduce lung cancer metastasis and recurrence by inhibiting the JAK2/STAT3 pathway, downregulating the presence of MDSCs, upregulating the proportion of DCs, and promoting the polarization of M2 macrophages to M1 macrophages. These changes enhance the anti-tumor immune response, contributing to the reduction of lung cancer metastasis and recurrence.https://doi.org/10.1177/15347354251324650 |
| spellingShingle | Yizhao Du MD Yongming Zhou PhD Lijing Jiao PhD Wenxiao Yang PhD Ling Xu PhD Hailun Zhou MD Jingwen Zhao MD Quanyao Li MD Yang Han MD Yabin Gong PhD Qin Wang PhD GuBenPeiYuan Formula Inhibits Lung Cancer Metastasis by Suppressing Myeloid-Derived Suppressor Cells and Related Immune Cells Integrative Cancer Therapies |
| title | GuBenPeiYuan Formula Inhibits Lung Cancer Metastasis by Suppressing Myeloid-Derived Suppressor Cells and Related Immune Cells |
| title_full | GuBenPeiYuan Formula Inhibits Lung Cancer Metastasis by Suppressing Myeloid-Derived Suppressor Cells and Related Immune Cells |
| title_fullStr | GuBenPeiYuan Formula Inhibits Lung Cancer Metastasis by Suppressing Myeloid-Derived Suppressor Cells and Related Immune Cells |
| title_full_unstemmed | GuBenPeiYuan Formula Inhibits Lung Cancer Metastasis by Suppressing Myeloid-Derived Suppressor Cells and Related Immune Cells |
| title_short | GuBenPeiYuan Formula Inhibits Lung Cancer Metastasis by Suppressing Myeloid-Derived Suppressor Cells and Related Immune Cells |
| title_sort | gubenpeiyuan formula inhibits lung cancer metastasis by suppressing myeloid derived suppressor cells and related immune cells |
| url | https://doi.org/10.1177/15347354251324650 |
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