三阴性乳腺癌(TNBC)是乳腺癌的一个主要亚型，目前临床上治疗药物有限。表皮生长因子受体（EGFR）被报道在多种TNBC细胞中高表达。苍蒿素是许多临床传统中药制剂中的有效成分，如德力生注射液、艾迪注射液、白砒和维生素B6注射液。以往的研究表明，苍蒿素对多种肿瘤具有满意的药理活性。本研究旨在通过靶向EGFR研究苍蒿素在TNBC治疗中的治疗潜力，并阐述其新颖调节因子miR-607。通过4T1小鼠模型评估苍蒿素对乳腺癌的体内疗效，然后通过MTT、克隆形成和AnnexinV-PE/7AAD染色评估苍蒿素对TNBC细胞的影响。应用细胞膜色谱、RT-PCR、Western blotting、MTT等验证苍蒿素作用于EGFR。通过荧光酶报告试验、RT-PCR、Western blotting、免疫荧光染色试验探讨该机制的研究。苍蒿素通过靶向EGFR抑制TNBC细胞生长并诱导凋亡。miR-607是一种新颖的EGFR调控因子，对TNBC细胞行为具有抑制功能。机制研究显示，苍蒿素阻断了下游PI3K/AKT/mTOR和ERK/MAPK信号通路。我们的结果揭示了通过miR-607介导的EGFR下调，苍蒿素可能作为TNBC治疗的潜在候选药物。© 2023. BioMed Central Ltd.,属于Springer Nature的一部分。

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.© 2023. BioMed Central Ltd., part of Springer Nature.