Division of Pharmacotherapy, Faculty of Pharmacy, Kindai University, Kowakae, Higashiosaka 577-8502, Japan.
Sakai City Medical Center, Department of Pharmacy, Sakai 593-8304, Japan.
Int J Mol Sci. 2022 Aug 4;23(15):8681. doi: 10.3390/ijms23158681.
Triple-negative breast cancer (TNBC) has the poorest prognosis of all breast cancer subtypes. Recently, the activation of NF-κB, which is involved in the growth and survival of malignant tumors, has been demonstrated in TNBC, suggesting that NF-κB may serve as a new therapeutic target. In the present study, we examined whether dimethyl fumarate (DMF), an NF-κB inhibitor, induces apoptosis in TNBC cells and enhances the apoptosis-inducing effect of paclitaxel and adriamycin. Cell survival was analyzed by the trypan blue assay and apoptosis assay. Protein detection was examined by immunoblotting. The activation of NF-κB p65 was correlated with poor prognosis in patients with TNBC. DMF induced apoptosis in MDA-MB-231 and BT-549 cells at concentrations that were non-cytotoxic to the normal mammary cell line MCF-10A. Furthermore, DMF inhibited NF-κB nuclear translocation and Survivin, XIAP, Bcl-xL, and Bcl-2 expression in MDA-MB-231 and BT-549 cells. Moreover, DMF enhanced the apoptosis-inducing effect of paclitaxel and adriamycin in MDA-MB-231 cells. These findings suggest that DMF may be an effective therapeutic agent for the treatment of TNBC, in which NF-κB is constitutively active. DMF may also be useful as an adjuvant therapy to conventional anticancer drugs.
三阴性乳腺癌（TNBC）是所有乳腺癌亚型中预后最差的。最近，在 TNBC 中已经证实了 NF-κB 的激活，NF-κB 参与恶性肿瘤的生长和存活，这表明 NF-κB 可能成为新的治疗靶点。在本研究中，我们研究了 NF-κB 抑制剂富马酸二甲酯（DMF）是否诱导 TNBC 细胞凋亡，并增强紫杉醇和阿霉素的凋亡诱导作用。通过台盼蓝检测和凋亡检测分析细胞存活率。通过免疫印迹检测蛋白质检测。NF-κB p65 的激活与 TNBC 患者的不良预后相关。DMF 在浓度下诱导 MDA-MB-231 和 BT-549 细胞凋亡，而对正常乳腺细胞系 MCF-10A 无细胞毒性。此外，DMF 抑制 MDA-MB-231 和 BT-549 细胞中的 NF-κB 核易位以及 Survivin、XIAP、Bcl-xL 和 Bcl-2 的表达。此外，DMF 增强了 MDA-MB-231 细胞中紫杉醇和阿霉素的凋亡诱导作用。这些发现表明，DMF 可能是一种有效的治疗 TNBC 的治疗剂，其中 NF-κB 是组成性激活的。DMF 也可能作为常规抗癌药物的辅助治疗剂。
