Animal Experimental Study on Tetrandrine Combined with Arsenic Trioxide for Breast Cancer Treatment

Abstract

Objective: To investigate the therapeutic effects of tetrandrine and arsenic trioxide (ATO) on breast cancer using a nude mouse xenograft model. Methods: A breast cancer xenograft model was established in nude mice using the MDA-MB-435S cell line. The mice were divided into treatment groups as follows: Tet group (tetrandrine), ATO group (arsenic trioxide), Tet+ATO group (combination therapy), CDDP group (cisplatin), and CON group (normal saline control). After 4 weeks of treatment, the therapeutic effects and potential mechanisms of the different drugs were evaluated through gross observation, histological examination, and immunohistochemical analysis of tumor and lung tissues. Results: Compared with the control group, tumor volume and mass were significantly reduced in the CDDP, Tet, ATO, and Tet+ATO groups (P < 0.05). The Tet+ATO group showed significantly greater reduction in tumor volume and mass than the Tet or ATO alone groups, though these values were higher than those in the CDDP group (P < 0.05). Gross examination revealed numerous gray-white nodules in the lungs of all control animals. Fewer nodules were observed in the Tet (4/8) and ATO (5/8) groups, while the CDDP (1/8) and Tet+ATO (3/8) groups exhibited markedly fewer nodules than the CON, Tet, and ATO groups. Immunohistochemistry showed significantly decreased MMP2 expression in the tumors of all drug-treated groups compared with the control, while MMP9 expression was increased primarily in fibrotic and granulation tissue areas. VEGF and CD31 expression were significantly lower in the CDDP and Tet+ATO groups than in the control. Conclusion: Tetrandrine, arsenic trioxide injection, and their combination all inhibited tumor growth and metastasis. The combined use of tetrandrine and arsenic trioxide reduced the required dosage of arsenic trioxide without compromising its inhibitory effect on breast cancer growth, while also decreasing the incidence of lung metastasis. The antitumor mechanism of the combination therapy is associated with the regulation of tumor angiogenesis and extracellular matrix remodeling.