RESUMO
OBJECTIVE: It has been suggested that Bisphenol A (BPA), a high-production-volume industrial chemical, can accelerate the development of various type of cancers. However, the effect of BPA on osteosarcoma and the underlying mechanisms are yet to be established. Therefore, in this study we tried to explore the carcinogenic effects of BPA on osteosarcoma and the underlying mechanism. METHODS: SaOs-2 cancer cell line was used to treat with BPA at the doses of 0.1, 1, 10 µM DGLAP5 knockdown and overexpression methods were constructed by using adenovirus mediated transfection, and the functional analysis of DGLAP5 was investigated to evaluate the carcinogenic effect of BPA on osteosarcoma through DLGAP5. Xenograft and metastatic mouse model were used to evaluate in vivo experiments. RESULTS: In this study, BPA at 10 µM promoted the proliferation, migration and invasion in vitro, and accelerate the progression and metastasis in vivo. Also, exposure to BPA was associated with poor survival of osteosarcoma in mice. In addition, we observed that BPA at 10 µM significantly increased the expression of DGLAP5 in osteosarcoma. Silencing DGLAP5 could reverse the effect of BPA on proliferation, migration and invasion. Mechanically, BPA promoted IL-6, JAK2, and STAT3 expression and promoted tumor progression in an IL-6-dependent manner through up-regulation of DLGAP5. CONCLUSION: Our findings demonstrated that BPA could promote the proliferation, migration, invasion of osteosarcoma cells and related to poor survival in a mouse model. DLGAP5 is one of the most critical targets of BPA to act as a carcinogen through IL-6/JAK2/STAT3 signaling pathway.
Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Camundongos , Animais , Interleucina-6/genética , Interleucina-6/metabolismo , Movimento Celular , Osteossarcoma/induzido quimicamente , Osteossarcoma/genética , Transdução de Sinais , Carcinogênese/induzido quimicamente , Carcinogênese/genética , Neoplasias Ósseas/induzido quimicamente , Neoplasias Ósseas/genética , Proliferação de Células , Linhagem Celular Tumoral , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/farmacologia , Proteínas de Neoplasias/uso terapêutico , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Janus Quinase 2/farmacologia , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/farmacologiaRESUMO
The autoimmune disease known as rheumatoid arthritis (RA) has been linked to the deterioration of bone. Bone erosion is a hallmark of RA and is linked to the severity of the disease as well as a poor functional result. Erosion of periarticular cortical bone is a common feature seen on plain radiographs of patients with RA. This characteristic feature is the result of excessive bone resorption and inadequate formation of bone. It has been determined that there is a complex interaction between the inflammatory condition seen in RA and bone destruction. Increased knowledge of the pathways and other mechanisms involved in osteoclastogenesis has resulted from advances in both animal and clinical investigations. Also, Biological and targeted medicines have modified RA's bone metabolism. Here, we provide a narrative overview of the literature on the pathomechanisms of bone structure involved in biological and targeted treatments for RA and also, the clinical implications of disease-modifying antirheumatic drugs (DMARDs) are discussed. In light of the fact that these newer treatments present patients with RA with new possibilities for disease improvement and symptom control, it is imperative that additional rigorous evidence be gathered to provide a clinical reference for both patients and their treating physicians.
