过氧化物酶体增殖物激活受体γ
上皮-间质转换
SMAD公司
癌症研究
基因敲除
三阴性乳腺癌
波形蛋白
信号转导
扭曲转录因子
生物
化学
转移
乳腺癌
内科学
过氧化物酶体增殖物激活受体
医学
受体
细胞生物学
癌症
免疫组织化学
细胞凋亡
生物化学
作者
Xuemei Huang,Zhiqin Jia,Xiangyue Li,Zhilan Hu,Xiaolan Yu,Jiyi Xia
摘要
Triple-negative breast cancer (TNBC) accounts for 10-20% of all human ductal adenocarcinomas and has a poor prognosis relative to other subtypes because of its high propensity to develop metastases. Here, the anticancer effects of asiaticoside (AC) against TNBC and the possible underlying mechanism were examined. We found that AC inhibited the TGF-β1 expression and the SMAD2/3 phosphorylation in TNBC cells, thereby impairing the TGF-β/SMAD signaling. AC inhibited the migration, invasion, and epithelial-mesenchymal transition (EMT) of TNBC cells by suppressing the TGF-β/SMAD signaling. Meanwhile, AC inhibited the lung metastasis of TNBC cells in vivo and the expression of p-SMAD2/3 and vimentin, and increased the expression of E-cadherin and ZO-1 in the lung. Peroxisome proliferator activated receptor gamma (PPARG) was identified as a potential target of AC. AC increased PPARG expression, while PPARG knockdown attenuated the therapeutic effect of AC. AC-mediated PPARG overexpression suppressed the transcription of P2X purinoceptor 7 (P2RX7). The restoration of P2RX7 reversed the therapeutic effect of AC. These results suggested that AC blocked P2RX7-mediated TGF-β/SMAD signaling by increasing PPARG expression, thereby suppressing EMT in TNBC.
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