RESUMO
Disordered copper metabolism plays a critical role in the development of various cancers. As a nanomedicine containing copper, cuprous oxide nanoparticles (CONPs) exert ideal antitumor pharmacological effects in vitro and in vivo. Prostate cancer is a frequently diagnosed male malignancy prone to relapse, and castration resistance is the main reason for endocrine therapy failure. However, whether CONPs have the potential to treat castration-resistant prostate cancer is still unknown. Here, using the castration-resistant PC-3 human prostate cancer cell line as a model, we report that CONPs can selectively induce apoptosis and inhibit the proliferation of cancer cells in vitro and in vivo without affecting normal prostate epithelial cells. CONPs can also attenuate the stemness of cancer cells and inhibit the Wnt signaling pathway, both of which highlight the great potential of CONPs as a new clinical castration-resistant prostate cancer therapy.
Assuntos
Antineoplásicos/farmacologia , Cobre/farmacologia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cobre/química , Humanos , Masculino , Camundongos Nus , Nanopartículas/química , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Neoplasias de Próstata Resistentes à Castração/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To study the effect of Ligustrazine on type I, III collagen synthesis in lung tissue of silica-treated rat. METHODS: The 128 experimental rats were randomly divided into control, silica and Ligustrazine group. 1ml silica (50g/L) was injected intratracheally in silica group and Ligustrazine group, while Ligustrazine group were injected intraperitoneally 50mg/(kg x d) Ligustrazine. Samples were collected on the 1st, 3rd, 7th, 14th, 21st, 28th day after injected silica. Type I , III collagen on paraffin-embedded lung sections were stained with sirius red, detected by polarized light microscopy and quantified by Image-Pro Plus. RESULTS: On the 3rd day after silica instillation, type III collagen began to appear, while type I collagen formed on the 7th day. Thereafter Type I, III collagen increased progressively. Compared with control group, type I, III collagen expression of silica group increased. At different time points type I, III collagen expression of Ligustrazine group decreased than silica group. There was significant difference of type I collagen area percentage on the 7th, 14th, 28th day, type III collagen area percentage on the 28th day between Ligustrazine group and silica group. CONCLUSION: Silica dioxide could induce the increase of type I, III collagen production in lung tissue, and their stages are different. Ligustrazine could suppress type I, III collagen production in lung tissue of silica-treated rat, and it's mechanism would be studied.