Department of Oncology, Nanjing First Hospital, NanJing Medical University, Nanjing, China.
Clinical Research Center, Xuyi People's Hospital, Xuyi, China.
J Cell Mol Med. 2018 Nov;22(11):5220-5230. doi: 10.1111/jcmm.13719. Epub 2018 Sep 4.
Oestrogen receptor (ER) is expressed in approximately 60%-70% of human breast cancer. Clinical trials and retrospective analyses have shown that ER-positive (ER+) tumours are more tolerant to chemotherapeutic drug resistance than ER-negative (ER-) tumours. In addition, isobavachalcone (IBC) is known as a kind of phytoestrogen with antitumour effect. However, the underlying mechanism of IBC in ER+ breast cancer needs to be elucidated further. Our in vitro experiments showed that IBC could attenuate 17β-estradiol (E )-induced paclitaxel resistance and that E could stimulate CD44 expression in ER+ breast cancer cells but not in ER- cells. Meanwhile, E could promote ERα expression to render ER+ breast cancer cells resistant to paclitaxel. Furthermore, we established paclitaxel-resistant breast cancer cell lines and determined the function of ERα in the enhancement of paclitaxel resistance via the regulation of CD44 transcription. IBC down-regulated ERα and CD44 expression and thus inhibited tumour growth in paclitaxel-resistant xenograft models. Overall, our data demonstrated for the first time that IBC could decrease CD44 expression level via the ERα pathway and make ER+ breast cancer cells sensitive to paclitaxel treatment.
雌激素受体（ER）在大约 60%-70%的人类乳腺癌中表达。临床试验和回顾性分析表明，ER 阳性（ER+）肿瘤比 ER 阴性（ER-）肿瘤对化疗药物耐药性更耐受。此外，异甘草素（IBC）被认为是一种具有抗肿瘤作用的植物雌激素。然而，IBC 在 ER+乳腺癌中的作用机制尚需进一步阐明。我们的体外实验表明，IBC 可以减弱 17β-雌二醇（E）诱导的紫杉醇耐药，E 可以刺激 ER+乳腺癌细胞但不能刺激 ER-细胞中 CD44 的表达。同时，E 可以促进 ERα 的表达，使 ER+乳腺癌细胞对紫杉醇产生耐药性。此外，我们建立了紫杉醇耐药的乳腺癌细胞系，并通过调节 CD44 转录来确定 ERα 在增强紫杉醇耐药性中的作用。IBC 下调 ERα 和 CD44 的表达，从而抑制紫杉醇耐药异种移植模型中的肿瘤生长。总的来说，我们的数据首次表明，IBC 可以通过 ERα 途径降低 CD44 的表达水平，使 ER+乳腺癌细胞对紫杉醇治疗敏感。
