RESUMO
Human pituitary adenoma is one of the most common intracranial tumors with an incidence as high as 16.7%. Recent evidence has hinted a relationship between growth factors of pituitary or hypothalamic origin and proliferation of human pituitary adenoma cells. This study explores the effects of small interfering RNA-mediated silencing of basic fibroblast growth factor gene on the proliferation, migration, and invasion of human pituitary adenoma cells. Human pituitary adenoma tissues were collected to obtain human pituitary adenoma cells. The basic fibroblast growth factor silencing interference plasmid was constructed, and the human pituitary adenoma cells were transfected and assigned as basic fibroblast growth factor-small interfering RNA, negative control-small interfering RNA, and blank groups. The quantitative real-time polymerase chain reaction and Western blotting were carried out to detect the expression of basic fibroblast growth factor, pituitary tumor transforming gene, vascular endothelial growth factor, cluster of differentiation 147, and matrix metalloproteinase 9. Cell Counting Kit-8 assay was conducted to observe cell proliferation at 0, 24, 48, and 72 h. Flow cytometry was used to determine cell cycle. Transwell and scratch test were applied to detect the invasion and migration of pituitary adenoma cells. Protein kinase C activity was detected. In comparison with the blank group, the basic fibroblast growth factor-small interfering RNA group showed reduced messenger RNA and protein expression of basic fibroblast growth factor, reduced cell viability at 24, 48, and 72 h, increased cells in G0/G1 stage, declined cells in S and G2/M stages, decreased number of cell migration, shortened migrating distance, reduced protein kinase C activity, and decreased expression of pituitary tumor transforming gene, vascular endothelial growth factor, cluster of differentiation 147, and matrix metalloproteinase 9. However, the negative control-small interfering RNA group had no evident differences in basic fibroblast growth factor expression, cell viability, cell cycle, number of cell migration, migrating distance, protein kinase C activity, and expression of pituitary tumor transforming gene, vascular endothelial growth factor, cluster of differentiation 147, and matrix metalloproteinase 9 compared with the blank group. The study provides evidence that small interfering RNA-mediated silencing of basic fibroblast growth factor gene inhibits the proliferation, migration, and invasion of human pituitary adenoma cells.
Assuntos
Proliferação de Células/genética , Fator 2 de Crescimento de Fibroblastos/genética , Invasividade Neoplásica/genética , Neoplasias Hipofisárias/genética , Apoptose/genética , Movimento Celular , Fator 2 de Crescimento de Fibroblastos/antagonistas & inibidores , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Invasividade Neoplásica/patologia , Neoplasias Hipofisárias/patologia , RNA Interferente Pequeno/genéticaRESUMO
OBJECTIVE: To observe the short-term efficacy of Pipeline embolization divice (PED) for the treatment of complex intracranial aneurysms. METHODS: The clinical data of 29 consecutive patients with 32 intracranial aneurysms treated with PED between April 2015 to September 2016 were analyzed retrospectively. There were 3 small aneurysm, 15 large aneurysms, 8 giant aneurysms, 5 fusiform ayneurysms and 1 recidivation. The vessels include 25 anterior circulation and 4 posterior circulation. RESULTS: We treated 31 aneurysms with 30 PEDs and all of the stents were implanted successfully. 1 case of single aneurysm was multiple divices implanted and 1 case of 3 aneurysms were treated by single PED. 12 of the 29 patients were implanted PED only, 17 were implanted PED with coils, 2 underwent balloon remodeling after the PED implanted. The ostia of 19 ophthalmic arteries, 10 posterior communicating arteries, 4 posterior inferior cerebellar arteries and 1 anterior cerebral artery were covered by PED during procedures; 1 ophthalmic arteries and 1 posterior communicating artery disappeared, no branch vessels occlusion and parent artery stenosis occurred.Hemorrhagic complacations occurred in 2 patients, 2 hours and 5 days after procedure respectively. Radiographic follow-up examnations were carried out in 24 patients and revealed complete occlusion in 21 patients, uncomplete occlusion in 3 patients. No neurological injure occurred in 27 patients who received a clinical follow-up. CONCLUSION: PED provide a safe and effective methord for the treatment of intracranial complex aneurysms like wide-neck aneurysms, fusiform aneurysms, giant aneurysms in low risk of procedural complications and high rates of aneurysm occlusion.
Assuntos
Embolização Terapêutica/instrumentação , Procedimentos Endovasculares/instrumentação , Aneurisma Intracraniano/terapia , Stents , Adolescente , Adulto , Idoso , Embolização Terapêutica/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Feminino , Seguimentos , Humanos , Aneurisma Intracraniano/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Stents/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: This study was designed to explore how miR-145 regulates the mTOR signaling pathway in invasive pituitary adenoma (IPA) by targeting AKT3. METHODS: A total of 71 cases of IPA tissues and 66 cases of non-IPA tissues were obtained in this study. In vitro, the IPA cells were assigned into blank control, empty plasmid, miR-145 mimic, miR-145 inhibitor, miR-145 mimic + rapamycin, miR-145 inhibitor + rapamycin and rapamycin groups. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were performed to detect the protein expressions of PI3K, AKT3, mTOR mRNA and the mRNA expression of miR-145 both in vivo and in vitro. Additionally, the S6K and RPS6 mRNA and protein expressions as well as the relative phosphorylation levels were determined in vitro. MTT assay, flow cytometry and transwell assay were used to testify the cell proliferation, apoptosis and invasion ability, respectively. RESULTS: The IPA tissues exhibited significantly lower expression of miR-145 but higher PI3K, AKT3 and mTOR mRNA and protein expressions when compared with the non-IPA tissues. Compared with the blank control and empty plasmid groups, the miR-145 mimic group showed significantly decreased PI3K, AKT3, mTOR, S6K and RPS6 mRNA and protein expressions as well as phosphorylation levels; besides, the IPA cell proliferation, migration and invasion ability were strongly inhibited, accompanied with the increased number of apoptotic cells. In the miR-145 inhibitor group, the PI3K, AKT3, mTOR, S6K and RPS6 mRNA and protein expressions as well as the phosphorylation levels were significantly increased; cell proliferation, migration and invasion ability were remarkably elevated, accompanied with reduced apoptotic cell number. CONCLUSION: The study demonstrates that miR-145 inhibits the mTOR signaling pathway to suppress the IPA cell proliferation and invasion and promotes its apoptosis by targeting AKT3.