Aqil Farrukh, Munagala Radha, Agrawal Ashish K, Jeyabalan Jeyaprakash, Tyagi Neha, Rai Shesh N, Gupta Ramesh C
UofL Health-Brown Cancer Center, 580 S. Preston St., Rm 304E, Baxter II Research Building, University of Louisville, Louisville, KY 40202, USA.
Department of Medicine, University of Louisville, Louisville, KY 40202, USA.
Cancers (Basel). 2021 Dec 13;13(24):6248. doi: 10.3390/cancers13246248.
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Due to the lack of drug-targetable receptors, chemotherapy is the only systemic treatment option. Although chemotherapeutic drugs respond initially in TNBC, many patients relapse and have a poor prognosis. Poor survival after metastatic relapse is largely attributed to the development of resistance to chemotherapeutic drugs. In this study, we show that bilberry-derived anthocyanidins (Anthos) can inhibit the growth and metastasis of TNBC and chemosensitize paclitaxel (PAC)-resistant TNBC cells by modulating the NF-κB signaling pathway, as well as metastatic and angiogenic mediators. Anthos administered orally significantly decreased MDA-MB-231 orthoxenograft tumor volume and led to lower rates of lymph node and lung metastasis, compared to control. Treatment of PAC-resistant MDA-MB-231Tx cells with Anthos and PAC in combination lowered the IC of PAC by nearly 20-fold. The combination treatment also significantly ( < 0.01) decreased the tumor volume in MDA-MB-231Tx orthoxenografts, compared to control. In contrast, Anthos and PAC alone were ineffective against MDA-MB-231Tx tumors. Our approach of using Anthos to inhibit the growth and metastasis of breast cancers, as well as to chemosensitize PAC-resistant TNBC, provides a highly promising and effective strategy for the management of TNBC.
三阴性乳腺癌（TNBC）是一种侵袭性乳腺癌亚型。由于缺乏可药物靶向的受体，化疗是唯一的全身治疗选择。尽管化疗药物最初对TNBC有反应，但许多患者会复发且预后较差。转移性复发后的低生存率很大程度上归因于对化疗药物产生耐药性。在本研究中，我们表明蓝莓衍生的花青素（Anthos）可通过调节NF-κB信号通路以及转移和血管生成介质来抑制TNBC的生长和转移，并使耐紫杉醇（PAC）的TNBC细胞对化疗敏感。与对照组相比，口服Anthos可显著降低MDA-MB-231原位移植瘤的体积，并降低淋巴结和肺转移率。用Anthos和PAC联合处理耐PAC的MDA-MB-231Tx细胞可使PAC的半数抑制浓度（IC）降低近20倍。与对照组相比，联合治疗还显著（<0.01）降低了MDA-MB-231Tx原位移植瘤的体积。相比之下，单独使用Anthos和PAC对MDA-MB-231Tx肿瘤无效。我们使用Anthos抑制乳腺癌生长和转移以及使耐PAC的TNBC对化疗敏感的方法，为TNBC的治疗提供了一种极有前景且有效的策略。
