School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta West Street, #54, Xi'an, 710061, Shaanxi, People's Republic of China.
State Key Laboratory of Shaanxi for Natural Medicines Research and Engineering, Xi'an, 710061, People's Republic of China.
J Transl Med. 2023 Sep 5;21(1):597. doi: 10.1186/s12967-023-04483-y.
Triple negative breast cancer (TNBC) is a major subtype of breast cancer, with limited therapeutic drugs in clinical. Epidermal growth factor receptor (EGFR) is reported to be overexpressed in various TNBC cells. Cantharidin is an effective ingredient in many clinical traditional Chinese medicine preparations, such as Delisheng injection, Aidi injection, Disodium cantharidinate and vitamin B6 injection. Previous studies showed that cantharidin had satisfactory pharmacological activity on a variety of tumors. In this study, we aimed to study the therapeutic potential of cantharidin for TNBC treatment by targeting EGFR, and expound its novel regulator miR-607.
The effect of cantharidin on breast cancer in vivo was evaluated by 4T1 mice model. Then the effects of cantharidin on TNBC cells was assessed by the MTT, colony formation, and AnnexinV-PE/7AAD staining. Cantharidin acts on EGFR were verified using the cell membrane chromatography, RT-PCR, Western blotting, MTT, and so on. Mechanistic studies were explored by dual-luciferase report assay, RT-PCR, western blotting, and immunofluorescence staining assay.
Cantharidin inhibited TNBC cell growth and induce apoptosis by targeting EGFR. miR-607 was a novel EGFR regulator and exhibited suppressive functions on TNBC cell behaviors. Mechanistic study showed that cantharidin blocked the downstream PI3K/AKT/mTOR and ERK/MAPK signaling pathway.
Our results revealed that cantharidin may be served as a potential candidate for TNBC treatment by miR-607-mediated downregulation of EGFR.
三阴性乳腺癌（TNBC）是乳腺癌的主要亚型，临床治疗药物有限。表皮生长因子受体（EGFR）在各种 TNBC 细胞中被报道过表达。斑蝥素是许多临床中药制剂的有效成分，如得力生注射液、艾迪注射液、斑蝥酸钠维生素 B6 注射液。先前的研究表明，斑蝥素对多种肿瘤具有令人满意的药理活性。在这项研究中，我们旨在通过靶向 EGFR 研究斑蝥素治疗 TNBC 的治疗潜力，并阐述其新型调节剂 miR-607。
通过 4T1 小鼠模型评估斑蝥素对乳腺癌的体内作用。然后通过 MTT、集落形成和 AnnexinV-PE/7AAD 染色评估斑蝥素对 TNBC 细胞的作用。使用细胞膜色谱、RT-PCR、Western blotting、MTT 等方法验证斑蝥素对 EGFR 的作用。通过双荧光素酶报告基因检测、RT-PCR、Western blotting 和免疫荧光染色实验等方法探索其作用机制。
斑蝥素通过靶向 EGFR 抑制 TNBC 细胞生长并诱导细胞凋亡。miR-607 是一种新型的 EGFR 调节剂，对 TNBC 细胞行为具有抑制作用。机制研究表明，斑蝥素阻断了下游的 PI3K/AKT/mTOR 和 ERK/MAPK 信号通路。
我们的研究结果表明，斑蝥素可能通过 miR-607 介导的 EGFR 下调作为 TNBC 治疗的潜在候选药物。
