RESUMEN
To examine the antitumor effects of gallic acid (GA) on osteosarcoma, two human osteosarcoma cell lines U-2OS and MNNG/HOS were treated by GA and subjected to cell proliferation and apoptosis assays. In addition, MNNG/HOS xenograft tumors were established in nude BALB/c mice to evaluate the anticancer capacity of GA in vivo. The results showed that GA inhibited the proliferation and induced the apoptosis of osteosarcoma cells, accompanied by the upregulation of p-38 activation and the downregulation of c-Jun N-terminal kinase (JNK) and extracellular signal regulated kinase (ERK1/2) activation. Additionally, p38 MAPK inhibitor abrogated GA-induced growth inhibition of osteosarcoma cells, whereas JNK or ERK1/2 inhibitors sensitized osteosarcoma cells to GA-induced growth inhibition. In vivo studies further showed that GA administration decreased xenograft tumor growth in a dose-dependent manner. Immunohistochemistry analysis demonstrated the downregulation of PCNA and CD31 expression and upregulation of apoptosis in MNNG/HOS tumor tissues following GA treatment. This study demonstrates the antitumor efficacy of GA for osteosarcoma that is mediated by the modulation of cell proliferation, apoptosis, and angiogenesis. Our findings suggest that GA could be a potent agent for osteosarcoma intervention.
Asunto(s)
Apoptosis/efectos de los fármacos , Neoplasias Óseas/tratamiento farmacológico , Ácido Gálico/farmacología , Sistema de Señalización de MAP Quinasas/genética , Proteína Quinasa 8 Activada por Mitógenos/genética , Osteosarcoma/tratamiento farmacológico , Animales , Antineoplásicos/farmacología , Neoplasias Óseas/enzimología , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Procesos de Crecimiento Celular/efectos de los fármacos , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Femenino , Humanos , MAP Quinasa Quinasa 4/antagonistas & inhibidores , MAP Quinasa Quinasa 4/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Proteína Quinasa 1 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Proteína Quinasa 8 Activada por Mitógenos/metabolismo , Osteosarcoma/enzimología , Osteosarcoma/genética , Osteosarcoma/patología , Ensayos Antitumor por Modelo de Xenoinjerto , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
INTRODUCTION: To systematically review the relationship between low pH in intervertebral discs and low back pain. MATERIAL AND METHODS: Electronic database (PubMed, ISI Web of Science, Cochrane Library, CINAHL, AMED, and China National Knowledge Infrastructure) searches and hand searching of conference proceedings were conducted. Two authors independently evaluated the methodological quality and abstracted relevant data according to standard criteria. Then the experimental methods and samples employed in the finally retrieved articles were assessed. RESULTS: We first retrieved 136 articles regarding pain and pH, and only 16 of them were mainly about low back pain and pH. Finally, 7 articles met our expectation to focus on the pathogenesis of low back pain caused by pH. In these 7 studies the authors held three opinions to explain the pathogenesis of low back pain in relation to low pH. First, low pH caused by lactate stimulates the muscle and increases the muscle tension, which causes low back pain. Second, low pH stimulates the nerve roots and produces the feeling of pain. Third, low pH changes the matrix metabolism, leading to neuronal death and low back pain. CONCLUSIONS: In this systematic review we propose a new hypothesis that low back pain may be caused by low pH based on the previous literature. Further experimental studies are necessary to verify our hypothesis. This hypothesis will promote our understanding of the pathogenesis of low back pain and the development of novel diagnostic and therapeutic approaches for low back pain.