RESUMEN
Cervical cancer (CC) is a common gynecological cancer and a leading cause of cancer-related deaths in women globally. Therefore, this study explores the action of microRNA-205 (miR-205) in the invasion, migration, and angiogenesis of CC through binding to tumor suppressor lung cancer 1 (TSLC1). Initially, the microarray analysis was used to select the candidate gene and the regulatory microRNA. Then, the target relationship between miR-205 and TSLC1 as well as the expression of miR-205, TSLC1, and p-Akt/total Akt in CC cells were determined. Afterwards, CC cell invasion and migration were detected after the treatment of miR-205 mimics/inhibitors and short hairpin RNA against TSLC1. After coculture of cancer cells and vascular endothelial cells, cell proliferation, tube formation, and microvessel density (MVD) were detected to determine the roles of miR-205 in angiogenesis. Finally, tumor growth in nude mice was measured in vivo. TSLC1 was determined as the candidate gene, which was found to be targeted and negatively regulated by miR-205. Then, downregulated miR-205 or forced TSLC1 expression inhibited invasion, migration, and angiogenesis in CC, corresponding to suppressed cell proliferation, tube formation, and expression of IL-8, VEGF, and bFGF, as well as the inhibited activation of the Akt signaling pathway. Furthermore, downregulation of miR-205 was found to exert an inhibitory role in tumor formation and MVD by elevating TSLC1 in CC in vivo. This study demonstrated that downregulated miR-205 inhibited cell invasion, migration, and angiogenesis in CC by inactivating the Akt signaling pathway via TSLC1 upregulation.
Asunto(s)
Molécula 1 de Adhesión Celular/metabolismo , Regulación hacia Abajo/genética , MicroARNs/genética , Neovascularización Patológica/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Neoplasias del Cuello Uterino/irrigación sanguínea , Neoplasias del Cuello Uterino/genética , Animales , Secuencia de Bases , Carcinogénesis/genética , Carcinogénesis/patología , Molécula 1 de Adhesión Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/metabolismo , Microvasos/patología , Modelos Biológicos , Invasividad Neoplásica , Unión Proteica , Regulación hacia Arriba/genética , Neoplasias del Cuello Uterino/patologíaRESUMEN
The study aims at statistical development of solid lipid nanoparticles (SLNs) loaded with topotecan hydrochloride for avoiding the drawbacks of conventional drug therapies used in cervical cancer. Twenty SLN batches were prepared using organic solvent evaporation method to provide response surface curves. Thereafter, optimized SLNs were obtained using numeric method based on desirability functions providing maximum drug loading and appropriate particle size. Physical characterization of optimized TPH loaded SLNs was performed in terms of particle size, zeta potential, transmission and scanning electron microscopic evaluation. Cytotoxicity studies were performed against cervical cancer cell lines, including cervical squamous cell carcinoma cell line (HeLa) and human squamous cell carcinoma cell line (SiHa). Also, Swiss mouse embryo fibroblast cells (3T3-L1) and African green monkey kidney epithelial (Vero) cells were used to evaluate biocompatibility in normal cells. As pronounced from the results, optimized SLNs may provide an attractive alternative to conventional cervical cancer drug products.
