Polydatin down-regulates the phosphorylation level of STAT3 and induces pyroptosis in triple-negative breast cancer mice with a high-fat diet
Min Liu, Yinan Li, Bingtan Kong, Gan‐Lin Zhang, Qing Zhang
Abstract
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: 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.