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 re...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（As_4O_6） has been demonstrated with an anticancer effect on squamous cell carcinoma and cervical cancer. However, there is no report about the relationship between As_4O_6 and HER-2 positive breast cancer. In the present study, we detected the inhibitory efficacy and mechanism of As_4O_6 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 As_4O_6. Meanwhile, the reverse transcription-PCR and western blotting were performed to investigate the mechanism of As_4O_6 on the migration and invasion of SKBR3 breast cancer cells. The results demonstrated that As_4O_6 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 As_4O_6 treatment. The mechanism revealed that As_4O_6 anticancer efficacy was related to HER-2/EGFR pathways. As_4O_6 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 As_4O_6 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 As_4O_6 might serve as potential anti-metastasis drug for clinical treatment of breast cancer.展开更多
文摘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（As_4O_6） has been demonstrated with an anticancer effect on squamous cell carcinoma and cervical cancer. However, there is no report about the relationship between As_4O_6 and HER-2 positive breast cancer. In the present study, we detected the inhibitory efficacy and mechanism of As_4O_6 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 As_4O_6. Meanwhile, the reverse transcription-PCR and western blotting were performed to investigate the mechanism of As_4O_6 on the migration and invasion of SKBR3 breast cancer cells. The results demonstrated that As_4O_6 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 As_4O_6 treatment. The mechanism revealed that As_4O_6 anticancer efficacy was related to HER-2/EGFR pathways. As_4O_6 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 As_4O_6 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 As_4O_6 might serve as potential anti-metastasis drug for clinical treatment of breast cancer.
