Xianlinglianxiafang Inhibited the growth and metastasis of triple-negative breast cancer via activating PPARγ/AMPK signaling pathway
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by high invasion and metastasis rates. Xian-Ling-Lian-Xia formula (XLLX) is a traditional Chinese medicine prescription widely used in China for treating TNBC. Clinical studies have shown that XLLX significa...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223009551 |
| _version_ | 1797744067364257792 |
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| author | Xiaojuan Yang Rui Yang Yang Zhang Youyang Shi Mei Ma Feifei Li Ying Xie Xianghui Han Sheng Liu |
| author_facet | Xiaojuan Yang Rui Yang Yang Zhang Youyang Shi Mei Ma Feifei Li Ying Xie Xianghui Han Sheng Liu |
| author_sort | Xiaojuan Yang |
| collection | DOAJ |
| description | Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by high invasion and metastasis rates. Xian-Ling-Lian-Xia formula (XLLX) is a traditional Chinese medicine prescription widely used in China for treating TNBC. Clinical studies have shown that XLLX significantly reduces the recurrence and metastasis rate of TNBC and improves disease-free survival. However, the potential molecular mechanisms of XLLX on TNBC are not clear yet. Here, we investigated the effects of XLLX on TNBC using a mouse model and tumor cell lines. The results showed that XLLX significantly inhibited the proliferation, migration, and invasion abilities of TNBC cell lines MDA-MB-231 and 4T1 in vitro, induced apoptosis, and regulated the expression of proliferation, apoptosis, and EMT marker proteins in tumor cells. In in vivo experiments, XLLX treatment significantly reduced the progression of TNBC tumors and lung metastasis. Transcriptomics reveals that XLLX treatment significantly enriched differentially expressed genes in the peroxisome proliferator-activated receptor gamma (PPARγ) and AMP-dependent protein kinase (AMPK) signaling pathways. The western blot results confirmed that XLLX significantly upregulated the protein expression of PPARγ and p-AMPK in TNBC cells, tumors, and lung tissues. It is noteworthy that GW9662 (a PPARγ inhibitor) and Compound C (an AMPK inhibitor) partially reversed the anti-proliferation and anti-metastasis effects of XLLX in TNBC cells. Therefore, XLLX may effectively inhibit the growth and metastasis of TNBC by activating the PPARγ/AMPK signaling pathway. |
| first_indexed | 2024-03-12T15:04:26Z |
| format | Article |
| id | doaj.art-77152e8fc7a44c628e5be61387ad871c |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-12T15:04:26Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-77152e8fc7a44c628e5be61387ad871c2023-08-13T04:52:49ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-09-01165115164Xianlinglianxiafang Inhibited the growth and metastasis of triple-negative breast cancer via activating PPARγ/AMPK signaling pathwayXiaojuan Yang0Rui Yang1Yang Zhang2Youyang Shi3Mei Ma4Feifei Li5Ying Xie6Xianghui Han7Sheng Liu8Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, Chinadepartment of breast surgery, Shanxi Provincial Cancer Hospital, Shanxi, ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Toxicology, School of Public Health, Lanzhou University, Lanzhou, ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Corresponding authors.Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Corresponding authors.Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Corresponding authors.Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by high invasion and metastasis rates. Xian-Ling-Lian-Xia formula (XLLX) is a traditional Chinese medicine prescription widely used in China for treating TNBC. Clinical studies have shown that XLLX significantly reduces the recurrence and metastasis rate of TNBC and improves disease-free survival. However, the potential molecular mechanisms of XLLX on TNBC are not clear yet. Here, we investigated the effects of XLLX on TNBC using a mouse model and tumor cell lines. The results showed that XLLX significantly inhibited the proliferation, migration, and invasion abilities of TNBC cell lines MDA-MB-231 and 4T1 in vitro, induced apoptosis, and regulated the expression of proliferation, apoptosis, and EMT marker proteins in tumor cells. In in vivo experiments, XLLX treatment significantly reduced the progression of TNBC tumors and lung metastasis. Transcriptomics reveals that XLLX treatment significantly enriched differentially expressed genes in the peroxisome proliferator-activated receptor gamma (PPARγ) and AMP-dependent protein kinase (AMPK) signaling pathways. The western blot results confirmed that XLLX significantly upregulated the protein expression of PPARγ and p-AMPK in TNBC cells, tumors, and lung tissues. It is noteworthy that GW9662 (a PPARγ inhibitor) and Compound C (an AMPK inhibitor) partially reversed the anti-proliferation and anti-metastasis effects of XLLX in TNBC cells. Therefore, XLLX may effectively inhibit the growth and metastasis of TNBC by activating the PPARγ/AMPK signaling pathway.http://www.sciencedirect.com/science/article/pii/S0753332223009551Triple-negative breast cancer (TNBC)XLLX formulaGrowth and metastasisPPARγ/AMPK signaling pathway |
| spellingShingle | Xiaojuan Yang Rui Yang Yang Zhang Youyang Shi Mei Ma Feifei Li Ying Xie Xianghui Han Sheng Liu Xianlinglianxiafang Inhibited the growth and metastasis of triple-negative breast cancer via activating PPARγ/AMPK signaling pathway Biomedicine & Pharmacotherapy Triple-negative breast cancer (TNBC) XLLX formula Growth and metastasis PPARγ/AMPK signaling pathway |
| title | Xianlinglianxiafang Inhibited the growth and metastasis of triple-negative breast cancer via activating PPARγ/AMPK signaling pathway |
| title_full | Xianlinglianxiafang Inhibited the growth and metastasis of triple-negative breast cancer via activating PPARγ/AMPK signaling pathway |
| title_fullStr | Xianlinglianxiafang Inhibited the growth and metastasis of triple-negative breast cancer via activating PPARγ/AMPK signaling pathway |
| title_full_unstemmed | Xianlinglianxiafang Inhibited the growth and metastasis of triple-negative breast cancer via activating PPARγ/AMPK signaling pathway |
| title_short | Xianlinglianxiafang Inhibited the growth and metastasis of triple-negative breast cancer via activating PPARγ/AMPK signaling pathway |
| title_sort | xianlinglianxiafang inhibited the growth and metastasis of triple negative breast cancer via activating pparγ ampk signaling pathway |
| topic | Triple-negative breast cancer (TNBC) XLLX formula Growth and metastasis PPARγ/AMPK signaling pathway |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223009551 |
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