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乳腺癌一直是女性最常见恶性肿瘤的研究焦点.虽然现在对HER-2阳性乳腺癌的治疗方法颇多,但是肿瘤耐药性和癌细胞远处转移仍是无法避免的难题.六氧化四砷(As4O6)已经被证实对鳞癌和子宫颈癌有一定的抗肿瘤效果,但是对HER-2阳性乳腺癌的研究未见报道.本研究旨在运用分子生物学方法探究As4O6对HER-2阳性乳腺癌SKBR3细胞的侵袭及迁移能力的抑制作用机制.通过As4O6干预SKBR3细胞,采用划痕实验、细胞迁移实验、Transwell侵袭实验和细胞黏附实验检测其对SKBR3细胞的迁移、侵袭及黏附能力的影响,同时,采用RT-PCR和Western blotting进一步阐明As4O6对乳腺癌SKBR3细胞侵袭转移的分子作用机制.结果显示,As4O6能有效抑制HER-2阳性乳腺癌SKBR3细胞的侵袭和迁移,并且SKBR3细胞的黏附能力在As4O6的干预下也有所减弱.实验结果表明,As4O6抗肿瘤效果与HER-2/EGFR信号通路有关,通过调节在HER-2/EGFR信号通路中的细胞因子(EGFR,HER-2,Akt,MMP-9)和其他关键分子,实现对HER-2阳性乳腺癌细胞迁移和侵袭的抑制作用.总之,As4O6抑制HER-2阳性乳腺癌SKBR3细胞的侵袭和迁移能力是通过HER-2/EGFR信号通路的负调节实现的.因此,As4O6可作为潜在的抗肿瘤转移药物和分子靶点抑制剂在乳腺癌的临床治疗中使用.“,”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.