ABSTRACT
AIM: To observe the influence of gold nanoparticles combined with Endostar (AuNPs-Endostar) on the melanoma lung metastasis of mice and the underlying mechanism.METHODS: C57BL/6 mice (n=24) were selected for constructing the model of spontaneous lung metastasis of melanoma B16-F10 cells.Subsequently, the mice were randomly divided into Endostar group, AuNPs group, AuNPs-Endostar group and model group.After the formation of melanoma, the mice in each group were injected with different drugs through tail vein for 0.1 mL daily.After 9 d, the mice were narcotized for cutting the tumors in situ.After the operation, they were raised for 2 weeks before killed for obtaining the lung tissues to observe the situation of the metastasis.HE staining was utilized for observing the necrosis status of the tumors in situ, while immunostaining was applied for testing the expression of CD31, carbonic anhydrase-IX (CA-IX), vimentin and zonula occludens-1 (ZO-1) in the tumors.RESULTS: Compared with model group, the pulmonary metastasis in the groups with medical treatment was obviously reduced.In AuNPs-Endostar group, the metastasis inhibition rate was the highest, and the tumor necrosis was also decreased obviously, with the significant reduction of CD31, CA-IX and vimentin expression in the tumors and significant increase in ZO-1 expression.CONCLUSION: Compared with using Endostar or AuNPs alone, the combination of AuNPs with Endostar significantly improves the curative effect of inhibiting the pulmonary metastasis of melanoma in the mice.The mechanism may be related to reducing the tumor angiogenesis, norma-lizing the blood vessels and improving tumor hypoxia, thus inhibiting the tumor epithelial-mesenchymal transition, increasing the tight junctions between tumor cells and decreasing the invasiveness.