ABSTRACT
Osteosarcoma (OS) is a malignant neoplasia in bone, characterized with main occurrence in teenagers. Calycosin (CC), a bioactive compound, is found to play potent pharmacological effects against cancer. Our previous study indicates CC-exerted benefits for anti-OS effect. However, further molecular mechanism behind this action needs to be investigated. In this study, human OS samples and clinical data were collected and used for further test and analysis. In addition, human osteosarcoma cell line (143B) and tumor-xenograft nude mice were used to evaluate antineoplastic activities of CC through a series of biochemical methods and immunoassays, respectively. Compared with non-OS controls, human OS samples showed increased levels of neoplastic microRNA-223 (miR-223), and elevated expressions of NF-κBp65, IκBα proteins in tumor cells. In cell culture study, CC-treated 143B cells showed reduced cell growth, increased lactic dehydrogenase (LD) content, and downregulated cellular miR-223 level. Immunolabeled cells of proliferating cell nuclear antigen, B-cell lymphoma 2 (Bcl-2), poly(ADP-ribose) polymerase (PARP) in CC treatments were decreased dose-dependently, while caspase-3 positive cells were elevated. Further, protein expressions of NF-κBp65, IκBα in CC-treated cells were downregulated. In addition, tumor-xenograft nude mice followed by CC treatments exhibited reductions of tumor mass, miR-223 levels, and Bcl-2, PARP-positive cells, as well as downregulations of NF-κBp65, IκBα protein expressions in OS samples. Taken together, these experimental findings reveal that CC exhibits potential pharmacological activities against OS through inducing apoptosis and inhibiting miR-223-IκBα signaling pathway in neoplastic cells.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Bone Neoplasms/drug therapy , Gene Expression Regulation, Neoplastic , Isoflavones/pharmacology , MicroRNAs/genetics , Osteosarcoma/drug therapy , Transcription Factor RelA/genetics , Adolescent , Animals , Bone Neoplasms/genetics , Bone Neoplasms/pathology , Bone Neoplasms/surgery , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Child , Female , Humans , L-Lactate Dehydrogenase/genetics , L-Lactate Dehydrogenase/metabolism , Male , Mice , Mice, Nude , MicroRNAs/metabolism , NF-KappaB Inhibitor alpha/genetics , NF-KappaB Inhibitor alpha/metabolism , Osteosarcoma/genetics , Osteosarcoma/pathology , Osteosarcoma/surgery , Poly(ADP-ribose) Polymerases/genetics , Poly(ADP-ribose) Polymerases/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Signal Transduction , Transcription Factor RelA/metabolism , Xenograft Model Antitumor AssaysABSTRACT
INTRODUCTION: chronic obstructive pulmonary disease (COPD) is 1 of the leading causes of morbidity and mortality worldwide; its economic and social burdens are substantial and increasing. Recent years, an increasing number of study has shown the promising advantage of Erchen decoction (ECD) combined with sanziyangqin decoction (SZYQD) in treating COPD. However, due to the lack of evidence, there is no specific method or suggestion, so it is necessary to provide a protocol for a systematic review on ECD combined with SZYQD for COPD and provide effective evidence for further clinical use. METHODS AND ANALYSIS: We will conduct a Computerized literature searches in the following databases: PubMed, MEDLINE, EMBASE, Cochrane Library, China national information network, China biomedical literature database (CBM), Chinese Scientific Journals Database and wanfang database, from their inception to June 2020, without restrictions of language. Study selection, data collection, and evaluation of the quality of evidence will be performed by 2 researchers independently, risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. All data analysis will be conducted by data statistics software Review Manager V.5.3. and Stata V.12.0. RESULTS: This study will systematically evaluate the effectiveness and safety of ECD combined with SZYQD for COPD. The results will be published in a peer-reviewed journal. CONCLUSION: This study will provide evidence from the current published RCTs of whether ERD combined with SZYQD is an effective and safe intervention for COPD. ETHICS AND DISSEMINATION: This study is a systematic review, the outcomes are based on the published evidence. In this study, no individual data from participants will be involved, so ethics approval is not required. OPEN SCIENCE FRAMEWORK(OSF)REGISTRATION NUMBER: August 19, 2020; osf.io/zxm24.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Pulmonary Disease, Chronic Obstructive/drug therapy , Drug Therapy, Combination , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/adverse effects , Humans , Randomized Controlled Trials as Topic , Research Design , Respiratory Function Tests , Meta-Analysis as TopicABSTRACT
BACKGROUND: To investigate the expression and role of PBRM1 in breast cancer, and to evaluate the clinical and prognostic significance of PBRM1 protein in patients with breast cancer. METHODS: The expression of PBRM1 was examined in breast cancer tissue and paired non-cancerous tissues by real-time PCR. Moreover, PBRM1 protein expression was evaluated by immunohistochemistry in 150 paraffin-embedded breast cancer specimens. The correlation between PBRM1 expression and clinicopathological features were statistically analyzed. RESULTS: The status of PBRM1 protein in breast cancer tissues is much lower than that in paracarcinoma tissues. Low PBRM1 expression was positively correlated with tumor stage (P =0.003) and lymph node metastasis (P =0.013). The overall (P =0.003) and recurrent-free survival (P =0.001) of the patients with high PBRM1 expression was significantly lower than the low PBRM1 expression group. Multivariate analysis showed that the expression of PBRM1 was an independent factor of overall survival for the patients with breast cancer (P =0.030). CONCLUSIONS: PBRM1 might involve in the development and progression of breast cancer as a tumor suppressor, and thereby may be a valuable prognostic marker for breast cancer patients.