RESUMO
As a malignant tumor, breast cancer is very prone to metastasis. Chemotherapy is one of the most common means for treating breast cancer. However, due to the serious metastasis and the poor targeting effect of traditional chemotherapeutic drugs, even after years of efforts, the therapeutic effect is still unsatisfied. Therefore, in this study, we constructed a kind of PFV modified epirubicin plus schisandrin B liposomes to solve the above disadvantages. In vitro experiments showed that the targeting liposomes with ideal physicochemical property could increase the cytotoxicity of MDA-MB-435S cells, destroy the formation of vasculogenic mimicry (VM), and inhibit tumor invasion and migration. Action mechanisms indicated that the inhibition of targeting liposomes on tumor metastasis was attributed to the regulation of the expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), vimentin (VIM), and E-cadherin (E-cad). In vivo pharmacodynamic experiments showed that the targeting liposomes could significantly improve the antitumor effect in mice. H&E staining and TUNEL results showed that the targeting liposomes could promote the apoptosis of tumor cells. Hence, the PFV modified epirubicin plus schisandrin B liposomes constructed in this study provided a new therapeutic strategy for breast cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Epirubicina/administração & dosagem , Lignanas/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Compostos Policíclicos/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Embrião de Galinha , Membrana Corioalantoide , Ciclo-Octanos/administração & dosagem , Feminino , Humanos , Lipossomos , Neoplasias Pulmonares/secundário , Camundongos , Invasividade Neoplásica , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, and the treatment effects are usually unsatisfactory. Vinorelbine (VRB) is extensively used in cancer treatment, but it has some disadvantages when used alone. PEGylated liposomes have been extensively used as a delivery carrier for antitumor drugs via prolonging the circulation time in the blood. PURPOSE: The nanostructured liposomes were designed and prepared for treating NSCLC. METHODS: In the liposomes, PEG was modified on the liposomal surface, DC-Chol was used as cationic materials, and VRB plus quinacrine were encapsulated in an aqueous core of the liposomes as an antitumor drug and an apoptosis-inducing agent, respectively. Evaluations were performed on A549 cells, tubular network formations and xenografts of the A549 cells. RESULTS: The PEGylated drugs-loaded cationic liposomes could significantly enhance cellular uptake and selectively accumulate in A549 cells, thus leading to show strongest antitumor efficacy to tumor cells and to tumor-bearing mice. Action mechanisms showed that the enhanced efficacy in treating NSCLC was related to activate caspase 9 and caspase 3, to activate Bax and P53, and to suppress Bcl-2 and Mcl-1. CONCLUSION: The PEGylated VRB plus quinacrine cationic liposomes showed a potential strategy for treating NSCLC.