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Polydatin down-regulates the phosphorylation level of STAT3 and induces pyroptosis in triple-negative breast cancer mice with a high-fat diet
BACKGROUND: To explore the impact of polydatin on mice with triple-negative breast cancer (TNBC) receiving a high-fat diet, as well as the underlying processes. METHODS: A total of 40 female Balb/c mice were randomly separated into 4 groups (4T1 + polydatin + fat diet group, 4T1 + high-fat diet grou...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8908165/ https://www.ncbi.nlm.nih.gov/pubmed/35280371 http://dx.doi.org/10.21037/atm-22-73 |
Sumario: | BACKGROUND: To explore the impact of polydatin on mice with triple-negative breast cancer (TNBC) receiving a high-fat diet, as well as the underlying processes. METHODS: A total of 40 female Balb/c mice were randomly separated into 4 groups (4T1 + polydatin + fat diet group, 4T1 + high-fat diet group, 4T1 + polydatin group, and 4T1 group). To establish the obese TNBC mouse model, TNBC was xenografted 1×10(5) 4T1 cells/50 µL per mouse at the right fourth mammary fat pad under anesthesia and the mice were fed a high fat diet. When the experiment was completed, total plasma cholesterol (TC) and cancer antigen (CA)15-3 were measured. The enzyme-linked immunosorbent assay (ELISA) method was used detect CA15-3. Oil red O staining was used to observe the morphological changes. Western blot analysis and reverse transcription polymerase chain reaction (RT-PCR) were used to detect the corresponding protein expression and the messenger RNA (mRNA) level. RESULTS: Polydatin decreased the degree of fatty liver, as determined by oil red O staining. The TC level in the 4T1 + fat diet group was significantly higher, and it was decreased in the 4T1 + polydatin group. The results of ELISA showed that compared with the 4T1 group, CA15-3 was significantly increased in the 4T1 + fat diet group, and polydatin was shown to significantly reduce the expression of CA15-3. Polydatin inhibited p-JAK2 and p-STAT3 mRNA and protein levels. Polydatin increased pyroptosis-related gene mRNA and protein level. CONCLUSIONS: We believe that polydatin can effectively reduce blood lipid levels in TNBC mice with a high-fat diet, and play an anticancer role in TNBC. The underlying mechanism may be related to the JAK2/STAT3 signaling pathway and pyroptosis in TNBC. Our results contribute to validating the traditional use of polydatin in the treatment of TNBC with hyperlipidemia. |
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