Effects of Resveratrol on Proliferation,Migration and Invasion of Triple-negative Breast Cancer Cells Through Tumor-associated Adipocytes and Its Mechanisms

YU Dongmin; HE Kang; LI Deping

doi:10.13730/j.issn.2097-2148.2025.11.002

Abstract：Objective To explore whether Resveratrol(Res)can affect the proliferation,migration and invasion of the triple-negative breast cancer cell line MDA-MB-231 by regulating the wingless-type MMTV integration site family(Wnt)/β-catenin signaling pathway through cancer-associated adipocytes(CAA).Methods MDA-MB-231 cells were treated with different concentrations of Res(25,50,100 umol/L),and the effect of Res on cell proliferation was detected by cell counting kit-8(CCK-8)after 24,48 and 72 h of culture;quantitative-polymerase chain reaction(qPCR)was used to detect the levels of fat markers;logarithmic growth MDA-MB-231 cells were divided into positive control group,nega-tive control group,CAA-CM group,Adi-CM group and CAA-CM+Res group.Fifteen BALB/c mice were divided into control group,high-fat diet group and high-fat diet+Res group based on whether they had high-fat and Res diets.Scratch test and Transwell test were used to verify the effect of Res on the migration and invasion of MDA-MB-231 cells.Hematoxylin-eosin(HE)staining were used to verify the effect of Res on CAA;Western blot and immunohistochemistry were used to verify the effect of Res on the expression of β-catenin and Cyclin D1 protein in CAA.Results ① Compared with Res concentration of 25 μmol/L,the cell survival number of 100 μmol/L concentration at 48 and 72 h decreased(all P＜0.05);compared with Res concentration of 50 μmol/L,the cell survival number of 100 μmol/L concentration at 72 h decreased(P＜0.05).Compared with 24 h,the cell survival number at different Res concentration at 48 and 72 h de-creased(all P＜0.05);compared with 48 h,the cell survival number at 72 h with Res concentration of 25 and 100 μmol/L decreased(all P＜0.05).② Compared with preadipocytes,the mRNA levels of hormone-sensitive lipase(HSL)and preadipocyte factor-1(Pref-1)in mature adipocytes were reduced,while the mRNA levels of peroxisome proliferator-acti-vated receptor γ(PPAR-γ)and CCAAT enhancer-binding protein α(C/EBP-α)increased(all P＜0.01).After mature adipocytes were co-cultured with MDA-MB-23 1 cells in a Transwell chamber,compared with mature adipocytes,the mR-NA levels of HSL and Pref-1 in CAA increased,while the mRNA levels of PPAR-γ and C/EBP-α decreased(all P＜0.01);and the mRNA levels of inflammatory factors interleukin-6(IL-6),IL-1β,C-C motif chemokine ligand 2(CCL2)and C-X-C motif chemokine ligand 8(CXCL8)in CAA increased(all P＜0.01).③ The migration rate and number of in-vasive cells in different groups were statistically significant(all P＜0.001).Compared with the positive control group,the migration rate and number of invasive cells in the negative control group,CAA-CM group,Adi-CM group and CAA-CM+Res group were reduced(all P＜0.05);compared with the negative control group,the migration rate and number of invasive cells in the CAA-CM group and Adi-CM group increased,and the number of invasive cells in the CAA-CM+Res group increased(all P＜0.05);compared with the CAA-CM group,the number of invasive cells in the Adi-CM group was reduced,and the migration rate and number of invasive cells in the CAA-CM+Res group were reduced(all P＜0.05);compared with Adi-CM group,the migration rate and number of invasive cells in the CAA-CM+Res group were reduced(all P＜0.05).④ Compared with the control group,the mice in the high-fat diet group had mature subcu-taneous adipocytes with increased diameter(P＜0.05);after Res intervention,compared with the high-fat diet group,the diameter of breast CAA in the high-fat diet+Res group was reduced(P＜0.05).⑤ Compared with the control group,the expression levels of β-catenin and Cyclin D1 in mice in the high-fat diet group increased,the protein expression levels of β-catenin and Cyclin D1 decreased in the high-fat diet+Res group(all P＜0.05).Compared with the high-fat group,the expression levels of β-catenin and Cyclin D1 in mice in the high-fat+Res group were reduced(all P＜0.05).Conclu-sion Res affects CAA regulation of the Wnt/β-catenin signaling pathway to inhibit the proliferation,migration and inva-sion of MDA-MB-231 cells.