Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, 650500, China.
Environ Sci Pollut Res Int. 2019 Jan;26(3):2353-2362. doi: 10.1007/s11356-018-3780-6. Epub 2018 Nov 22.
Selective estrogen receptor modulators such as tamoxifen (TAM) significantly reduce the risks of developing estrogen receptor-positive (ER+) breast cancer. Low concentrations (nanomolar range) of bisphenol A (BPA) shows estrogenic effects and further promotes the proliferation of hormone-dependent breast cancer cells. However, whether or not BPA can influence TAM-treatment resistance in breast cancer has not drawn much attention. In the current study, low concentrations of BPA reduced TAM-induced cytotoxicity of MCF-7 cells, which was proved by the suppression of cell apoptosis, transition of cell cycle from G1 to S phase, and upregulation of cyclin D1 and ERα. Simultaneously, the mRNA levels of estrogen-related receptor γ (ERRγ) and its coactivators, peroxisome proliferation-activated receptor γ coactivator-1α (PGC-1α), and PGC-1β, were increased. However, the similar effects were not observed in MDA-MB-231 cells. Our results indicated that low concentrations of BPA decreased the sensitivity of TAM in MCF-7 cells rather than in MDA-MB-231 cells. These different actions likely involved the interaction of relative receptors and coactivators. This study provided a possible support that the exposure of BPA in environmental media may potentially induce TAM resistance to breast cancer treatment.
选择性雌激素受体调节剂，如他莫昔芬（TAM），可显著降低雌激素受体阳性（ER+）乳腺癌的发病风险。低浓度（纳摩尔级）的双酚 A（BPA）具有雌激素作用，并进一步促进激素依赖性乳腺癌细胞的增殖。然而，BPA 是否会影响乳腺癌的 TAM 治疗耐药性尚未引起太多关注。在本研究中，低浓度的 BPA 降低了 MCF-7 细胞中 TAM 诱导的细胞毒性，这一点通过抑制细胞凋亡、细胞周期从 G1 期向 S 期的转变以及细胞周期蛋白 D1 和 ERα 的上调得到了证明。同时，雌激素相关受体 γ（ERRγ）及其共激活剂过氧化物酶体增殖物激活受体 γ 共激活剂-1α（PGC-1α）和 PGC-1β 的 mRNA 水平也升高了。然而，在 MDA-MB-231 细胞中没有观察到类似的效果。我们的研究结果表明，低浓度的 BPA 降低了 MCF-7 细胞而非 MDA-MB-231 细胞中 TAM 的敏感性。这些不同的作用可能涉及相对受体和共激活剂的相互作用。本研究提供了一个可能的支持，即环境介质中 BPA 的暴露可能潜在地诱导乳腺癌治疗中 TAM 的耐药性。
