Abstract:

Breast cancer is one of the most common female malignant tumors in the world. Although many therapeutic methods for HER-2 positive breast cancer have been developed, the drug resistance and distant metastasis still remain. Tetraarsenic oxide (As₄O₆) has been demonstrated with an anticancer effect on squamous cell carcinoma and cervical cancer. However, there is no report about the relationship between As₄O₆ and HER-2 positive breast cancer. In the present study, we detected the inhibitory efficacy and mechanism of As₄O₆ on the migration and invasion of SKBR3 breast cancer cells using molecular biological methods. The wound-healing assay, matrigel migration assay, transwell invasion assay and cell adhesion assay were used to assess the migration, invasion and adhesion of SKBR3 cells intervened by As₄O₆. Meanwhile, the reverse transcription-PCR and western blotting were performed to investigate the mechanism of As₄O₆ on the migration and invasion of SKBR3 breast cancer cells. The results demonstrated that As₄O₆ could efficiently inhibit the migration and invasion of SKBR3 cells, the HER-2 positive breast cancer cells, and the adhesion of SKBR3 cells was decreased after As₄O₆ treatment. The mechanism revealed that As₄O₆ anticancer efficacy was related to HER-2/EGFR pathways. As₄O₆ exerted its inhibitory effects on migration and invasion in HER-2 positive breast cancer cells by regulating the factors (EGFR, HER-2, Akt, MMP-9) in HER2/ EGFR signaling pathway and other key molecules. In conclusion, the present study indicated that As₄O₆ inhibited the invasion and migration process of HER-2 positive breast cancer SKBR3 cells by negatively regulating the HER-2/EGFR-mediated signaling pathway. These data provided evidence that As₄O₆ might serve as potential anti-metastasis drug for clinical treatment of breast cancer. 

Key words: HER-2 positive breast cancer, Tetraarsenic oxide, Migration, Invasion, Adhesion, Signaling pathway