ABSTRACT
Repurposing existing drugs for cancer therapy has become an important strategy because of its advantages, such as cost reduction, effect and safety. The present study was designed to investigate the antimelanoma effect and possible mechanisms of action of nebivolol, which is an approved and widely prescribed antihypertensive agent. In this study, we explored the effect of nebivolol on cell proliferation and cell activity in melanoma in vitro and the potential antimelanoma mechanism of nebivolol through a series of experiments, including the analysis of the effects with regard to cell apoptosis and metastasis. Furthermore, we evaluated the antimelanoma effect on xenograft tumor models and inspected the antimelanoma mechanism of nebivolol in vivo using immunohistochemical and immunofluorescence staining assays. As results in this work, in vitro , nebivolol possessed a strong activity for suppression proliferation and cell cycle arrest on melanoma. Moreover, nebivolol significantly induced cell apoptosis in melanoma through a mitochondrial-mediated endogenous apoptosis pathway. Additionally, nebivolol inhibited melanoma cell metastasis. More importantly, nebivolol exhibited significantly effective melanoma xenograft models in vivo , which related to the mechanism of apoptosis induction, proliferation inhibition, metastasis blocking and angiogenesis arrest. Overall, the data of the present study recommend that nebivolol holds great potential in application as a novel agent for the treatment of melanoma.
Subject(s)
Antihypertensive Agents , Apoptosis , Cell Proliferation , Melanoma , Nebivolol , Xenograft Model Antitumor Assays , Nebivolol/pharmacology , Nebivolol/therapeutic use , Animals , Humans , Melanoma/drug therapy , Melanoma/pathology , Apoptosis/drug effects , Cell Proliferation/drug effects , Mice , Antihypertensive Agents/pharmacology , Antihypertensive Agents/therapeutic use , Cell Line, Tumor , Mice, Nude , Cell Cycle Checkpoints/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Cell Movement/drug effectsABSTRACT
RATIONALE: Gerstmann-Sträussler-Scheinker syndrome (GSS) is a rare autosomal dominant disease caused by a mutation in the prion protein gene (PRNP) that is not well known among neurologists and is therefore easily misdiagnosed. PATIENT CONCERNS: : A 49-year-old man was admitted for the first time because of an unsteady walk with mogilalia for 1âyear. He underwent a cervical discectomy and a plate-screw fixation 6âmonths prior, although postoperative gait instability did not improve. DIAGNOSIS: Whole exome sequencing identified a pathogenic and heterozygous mutation in the PRNP 4âyears after onset. The patient was eventually diagnosed with GSS. INTERVENTIONS: Symptomatic treatment to improve cerebrocirculation and cerebrometabolism was provided. OUTCOMES: The neurological decline continued. The Mini-Mental State Examination and modified Rankin Scale scores changed from 19 to 11 and 2 to 5, respectively. Progressive cerebral and cerebellar atrophy on magnetic resonance imaging was observed. LESSONS: Cerebral and cerebellar atrophy are neuroimaging features symptomatic of GSS that become more apparent as the disease progresses. This atrophy is positively correlated with the severity of symptoms and reduced quality of life. Neurologists treating middle-aged patients with progressive ataxia, cognitive impairment or dysarthria, and brain atrophy need to consider the possibility of GSS.
