Cantharidin induces apoptosis of human triple negative breast cancer cells through mir-607-mediated downregulation of EGFR.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

Our results revealed that cantharidin may be served as a potential candidate for TNBC treatment by miR-607-mediated downregulation of EGFR.

• Authors: Tianfeng Yang, Runze Yu, Cheng Cheng, Jian Huo, Zhengyan Gong, Hanbing Cao, Yu Hu, Bingling Dai, Yanmin Zhang
• Journal: Journal of translational medicine (J Transl Med) Vol. 21 Issue 1 Pg. 597 (09 05 2023) ISSN: 1479-5876 [Electronic] England
• PMID: 37670360 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. BioMed Central Ltd., part of Springer Nature.

Chemical References

• Cantharidin
• Phosphatidylinositol 3-Kinases
• ErbB Receptors
• MicroRNAs
• EGFR protein, human

Topics

• Animals
• Mice
• Humans
• Triple Negative Breast Neoplasms
• Cantharidin
• Down-Regulation
• Phosphatidylinositol 3-Kinases
• ErbB Receptors
• Apoptosis
• MicroRNAs