Shuangshen Granules Suppress Myeloid-derived Suppressor Cell-mediated Lung Premetastatic Niche Development by Targeting Sphingosine-1-Phosphate Receptor-1/Signal Transducer, Activator of Transcription 3 Signaling
Background: Shuangshen granules (SSGs) are extensively utilized for the treatment of lung cancer in China and have been reported to possess tumor-protective and anti-metastatic effects. Therefore, it is crucial to understand the precise mechanism. Building upon the findings of our previous study, th...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2024-12-01
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| Series: | World Journal of Traditional Chinese Medicine |
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| Online Access: | https://journals.lww.com/10.4103/wjtcm.wjtcm_51_23 |
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| author | Rui Liu Jia-Qi Hu Xing Zhang Xiao-Yi Wu Hua-Min Wei Yuan-Chen Zhao Shu-Lin He Jing Yu Xin Qi Ying-Xia Pei Hong Chen Wei-Dong Li Bao-Jin Hua |
| author_facet | Rui Liu Jia-Qi Hu Xing Zhang Xiao-Yi Wu Hua-Min Wei Yuan-Chen Zhao Shu-Lin He Jing Yu Xin Qi Ying-Xia Pei Hong Chen Wei-Dong Li Bao-Jin Hua |
| author_sort | Rui Liu |
| collection | DOAJ |
| description | Background:
Shuangshen granules (SSGs) are extensively utilized for the treatment of lung cancer in China and have been reported to possess tumor-protective and anti-metastatic effects. Therefore, it is crucial to understand the precise mechanism. Building upon the findings of our previous study, the objective of the present study was to explore the impact of SSGs on the sphingosine-1-phosphate receptor-1 (S1PR1)/signal transducer and activator of transcription 3 (STAT3) axis, as well as the recruitment of myeloid-derived suppressor cells (MDSCs) during the formation of the premetastatic niches (PMNs).
Methods:
In a mouse xenograft model utilizing Lewis lung carcinoma (LLC) cells that express green fluorescent protein (GFP), the initiation of lung metastasis was monitored every three days until day 35 following transplantation. Lung metastasis, MDSC recruitment, the expression of PMN and S1PR1/STAT3 axis biomarkers, as well as the blood levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor-β (TGF-β) were assessed in the SSG treatment and control groups.
Results:
The LLC cells did not reach the lung until 14–17 days following subcutaneous implantation, which was concurrent with the formation of lung PMNs. SSG significantly postponed the initiation of lung metastasis and reduced the recruitment of MDSCs to the lung PMNs. SSG also suppressed the S1PR1/STAT3 axis in tumor tissues, bone marrow, and lung PMNs. Additionally, SSG suppressed the blood levels of GM-CSF and TGF-β, as well as the PMN markers, matrix metalloproteinase-9 and versican.
Conclusion:
Our findings suggested that SSG suppressed the development of MDSC-mediated PMNs by inhibiting the S1PR1/STAT3 axis, consequently postponing the initiation of lung metastasis. |
| format | Article |
| id | doaj-art-5beb3b2801e14c2db580c5e9a059fe4d |
| institution | Kabale University |
| issn | 2311-8571 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | World Journal of Traditional Chinese Medicine |
| spelling | doaj-art-5beb3b2801e14c2db580c5e9a059fe4d2025-01-16T08:49:39ZengWolters Kluwer Medknow PublicationsWorld Journal of Traditional Chinese Medicine2311-85712024-12-0110448549410.4103/wjtcm.wjtcm_51_23Shuangshen Granules Suppress Myeloid-derived Suppressor Cell-mediated Lung Premetastatic Niche Development by Targeting Sphingosine-1-Phosphate Receptor-1/Signal Transducer, Activator of Transcription 3 SignalingRui LiuJia-Qi HuXing ZhangXiao-Yi WuHua-Min WeiYuan-Chen ZhaoShu-Lin HeJing YuXin QiYing-Xia PeiHong ChenWei-Dong LiBao-Jin HuaBackground: Shuangshen granules (SSGs) are extensively utilized for the treatment of lung cancer in China and have been reported to possess tumor-protective and anti-metastatic effects. Therefore, it is crucial to understand the precise mechanism. Building upon the findings of our previous study, the objective of the present study was to explore the impact of SSGs on the sphingosine-1-phosphate receptor-1 (S1PR1)/signal transducer and activator of transcription 3 (STAT3) axis, as well as the recruitment of myeloid-derived suppressor cells (MDSCs) during the formation of the premetastatic niches (PMNs). Methods: In a mouse xenograft model utilizing Lewis lung carcinoma (LLC) cells that express green fluorescent protein (GFP), the initiation of lung metastasis was monitored every three days until day 35 following transplantation. Lung metastasis, MDSC recruitment, the expression of PMN and S1PR1/STAT3 axis biomarkers, as well as the blood levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor-β (TGF-β) were assessed in the SSG treatment and control groups. Results: The LLC cells did not reach the lung until 14–17 days following subcutaneous implantation, which was concurrent with the formation of lung PMNs. SSG significantly postponed the initiation of lung metastasis and reduced the recruitment of MDSCs to the lung PMNs. SSG also suppressed the S1PR1/STAT3 axis in tumor tissues, bone marrow, and lung PMNs. Additionally, SSG suppressed the blood levels of GM-CSF and TGF-β, as well as the PMN markers, matrix metalloproteinase-9 and versican. Conclusion: Our findings suggested that SSG suppressed the development of MDSC-mediated PMNs by inhibiting the S1PR1/STAT3 axis, consequently postponing the initiation of lung metastasis.https://journals.lww.com/10.4103/wjtcm.wjtcm_51_23lung metastasismyeloid-derived suppressor cellpremetastatic nicheshuangshen granulessphingosine-1-phosphate receptor-1/signal transducer activator of transcription 3 axis |
| spellingShingle | Rui Liu Jia-Qi Hu Xing Zhang Xiao-Yi Wu Hua-Min Wei Yuan-Chen Zhao Shu-Lin He Jing Yu Xin Qi Ying-Xia Pei Hong Chen Wei-Dong Li Bao-Jin Hua Shuangshen Granules Suppress Myeloid-derived Suppressor Cell-mediated Lung Premetastatic Niche Development by Targeting Sphingosine-1-Phosphate Receptor-1/Signal Transducer, Activator of Transcription 3 Signaling World Journal of Traditional Chinese Medicine lung metastasis myeloid-derived suppressor cell premetastatic niche shuangshen granules sphingosine-1-phosphate receptor-1/signal transducer activator of transcription 3 axis |
| title | Shuangshen Granules Suppress Myeloid-derived Suppressor Cell-mediated Lung Premetastatic Niche Development by Targeting Sphingosine-1-Phosphate Receptor-1/Signal Transducer, Activator of Transcription 3 Signaling |
| title_full | Shuangshen Granules Suppress Myeloid-derived Suppressor Cell-mediated Lung Premetastatic Niche Development by Targeting Sphingosine-1-Phosphate Receptor-1/Signal Transducer, Activator of Transcription 3 Signaling |
| title_fullStr | Shuangshen Granules Suppress Myeloid-derived Suppressor Cell-mediated Lung Premetastatic Niche Development by Targeting Sphingosine-1-Phosphate Receptor-1/Signal Transducer, Activator of Transcription 3 Signaling |
| title_full_unstemmed | Shuangshen Granules Suppress Myeloid-derived Suppressor Cell-mediated Lung Premetastatic Niche Development by Targeting Sphingosine-1-Phosphate Receptor-1/Signal Transducer, Activator of Transcription 3 Signaling |
| title_short | Shuangshen Granules Suppress Myeloid-derived Suppressor Cell-mediated Lung Premetastatic Niche Development by Targeting Sphingosine-1-Phosphate Receptor-1/Signal Transducer, Activator of Transcription 3 Signaling |
| title_sort | shuangshen granules suppress myeloid derived suppressor cell mediated lung premetastatic niche development by targeting sphingosine 1 phosphate receptor 1 signal transducer activator of transcription 3 signaling |
| topic | lung metastasis myeloid-derived suppressor cell premetastatic niche shuangshen granules sphingosine-1-phosphate receptor-1/signal transducer activator of transcription 3 axis |
| url | https://journals.lww.com/10.4103/wjtcm.wjtcm_51_23 |
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