College of Pharmacy, Duksung Women's University, Seoul, South Korea.
Front Endocrinol (Lausanne). 2020 Sep 15;11:560605. doi: 10.3389/fendo.2020.560605. eCollection 2020.
Triple-negative breast cancer (TNBC) is associated with a high mortality rate among women globally. TNBC shows a high rate of recurrence and distant metastasis. Particularly, the chemotherapy is limited because hormone therapy of breast cancer is ineffective. Thus, an effective chemotherapeutic agent is needed for tumor suppression. Chrysin-nanoparticles (chrysin-NPs) were investigated for their inhibitory effect on a MDA-MB-231-derived xenograft model. To gain insight into the underlying mechanisms, we conducted human matrix metalloproteinase (MMP) array, western blot, and immunohistochemistry analysis. Furthermore, imaging was used to monitor the chemotherapeutic efficacy of chrysin-NPs in a metastasis mouse model. Chrysin-NPs significantly inhibited the proliferation of MDA-MB-231 cells the PI3K/JNK pathway and induced cell death through the p53-apoptosis pathway, leading to delayed MDA-MB-231-derived tumor growth. Interestingly, chrysin-NPs significantly induced G protein-coupled estrogen receptor (GPER) expression, which suppresses MMPs and NF-κB expression. Chrysin-NPs acted as effective metastasis inhibitors. Our results suggest that chrysin-NPs may be used as an effective adjuvant formulation to inhibit TNBC progression.
三阴性乳腺癌（TNBC）与全球女性的高死亡率相关。TNBC表现出高复发率和远处转移率。特别是，由于乳腺癌的激素治疗无效，化疗受到限制。因此，需要一种有效的化疗药物来抑制肿瘤。白杨素纳米粒子（chrysin-NPs）因其对 MDA-MB-231 衍生的异种移植模型的抑制作用而受到研究。为了深入了解潜在的机制，我们进行了人类基质金属蛋白酶（MMP）阵列、western blot 和免疫组织化学分析。此外，还使用成像来监测 chrysin-NPs 在转移小鼠模型中的化疗效果。Chrysin-NPs 显著抑制了 MDA-MB-231 细胞的增殖， 通过 PI3K/JNK 途径诱导细胞死亡，并通过 p53 凋亡途径导致 MDA-MB-231 衍生肿瘤生长延迟。有趣的是，chrysin-NPs 显著诱导了 G 蛋白偶联雌激素受体（GPER）的表达，从而抑制了 MMPs 和 NF-κB 的表达。Chrysin-NPs 作为有效的转移抑制剂。我们的结果表明，chrysin-NPs 可作为抑制 TNBC 进展的有效辅助制剂。
