ABSTRACT
AIMS: Glioblastoma is one of the most invasive tumors of the central nervous system, and has a high degree of malignancy and poor prognosis. Harmine, an active ingredient extracted from perennial herbs, has been reported to have obvious antitumor effects on various tumors. However, the effects of harmine on glioblastoma growth remain unknown. We here explored the effects of harmine on glioblastoma and its underlying molecular mechanisms related to tumorigenesis. MATERIALS AND METHODS: CCK-8 and immunofluorescent assay were performed to measure anti-proliferative effect of harmine on U251-MG and U373-MG cells. Wound healing assay was performed to measure the effects of harmine on cell migration. qRT-PCR and western blot were performed to detect the protein/gene expression. BALB/c nude mice bearing U251-MG xenografts was used to measure the effects of harmine on the growth of glioblastoma in vivo. KEY FINDINGS: Harmine treatment significantly suppressed the proliferation of U251-MG and U373-MG cells in a dose and time-dependent way. Mechanistically, harmine reduced the basal and EGF-enhanced the phosphorylation level of FAK and AKT. Moreover, harmine inhibited the cell viability of U251-MG and U373-MG cells by downregulating the phosphorylation of the FAK/AKT pathway. Besides, harmine significantly suppressed the migration of U251-MG cells by suppressing the expression of MMP2, MMP9 and VEGF. Subsequently, orthotopic xenograft models revealed that harmine treatment dramatically inhibited the growth of glioblastoma in vivo. SIGNIFICANCE: In conclusion, these results suggest that harmine suppresses the proliferation and migration of U251-MG and U373-MG cells by inhibiting the FAK/AKT signaling pathway. Our findings elucidate harmine could be a promising drug for glioblastoma therapy.
Subject(s)
Glioblastoma/metabolism , Harmine/pharmacology , Animals , Brain Neoplasms/pathology , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , China , Focal Adhesion Kinase 1/metabolism , Glioblastoma/drug therapy , Harmine/metabolism , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Phosphorylation , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , Xenograft Model Antitumor Assays/methodsABSTRACT
Kin17 DNA and RNA binding protein (Kin17) is an extremely conserved nuclear protein that is almost expressed in every type of mammal cells. Recently, Kin17 has been implicated into the regulation of tumorigenesis of diverse human cancers. However, its functions in thyroid cancer (TC) are still largely unexplored. Kin17 mRNA and protein level were tested by qRT-PCR and western blot, respectively. Effects of Kin17 on TC cell proliferation were estimated by colony formation assay and flow cytometry analysis in vitro as well as by in vivo tumor growth experiment. TC cell migratory and invasive capacities were assessed via wound-healing and transwell experiments. Epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin and N-cadherin) and p38 MAPAK signaling pathway-related proteins (p-p38, p38, Cyclin D1, and p27) were examined via western blot. Kin17 was remarkably increased in TC tissue samples and cell lines at both mRNA and protein levels compared to normal tissue and control cell line. Knockdown of Kin17 obviously repressed TC cell proliferation, arrested cell cycle, and inhibited TC cell migration and invasion in vitro, while overexpression of Kin17 produced opposite effects. Kin17 knockdown suppressed p38 MAPK signaling pathway, while Kin17 overexpression activated this pathway. Treatment of p38 agonist (p79350) abolished the repressive effects of sh-Kin17 on TC cell proliferation, migration, and invasion, as well as on p38 pathway. Kin17 knockdown was also found to enhance the sensitivity of Doxorubicin of TC cells. In addition, Kin17 knockdown in vivo also markedly repressed TC tumor growth and p38 pathway. Kin17 functioned as an oncogene of TC by activating p38 MAPK signaling pathway.
Subject(s)
DNA-Binding Proteins/metabolism , Doxorubicin/pharmacology , RNA-Binding Proteins/metabolism , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/pathology , p38 Mitogen-Activated Protein Kinases/metabolism , Animals , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , DNA-Binding Proteins/genetics , Humans , Male , Mice, Nude , Neoplasm Invasiveness , RNA-Binding Proteins/genetics , Signal Transduction , Thyroid Neoplasms/genetics , Topoisomerase II Inhibitors/pharmacology , Xenograft Model Antitumor Assays , p38 Mitogen-Activated Protein Kinases/geneticsABSTRACT
This study evaluated the predictive value of the preoperative albumin/globulin ratio (AGR) in laryngeal squamous cell carcinoma (LSCC) retrospectively, which has not been reported before. The current study enrolled 241 newly diagnosed LSCC patients in the Second Affiliated Hospital of Nanchang University between January 2005 and December 2010. The optimal AGR cut-off value for overall survival (OS) was determined to be 1.28. Univariate survival analysis identified sex, low AGR, T classification, histological grade and nodal metastasis as factors associated with poor OS. Additionally, a low AGR, T classification, nodal metastasis, and histological grade were associated with poor disease-free survival (DFS) in LSCC patients. In multivariate survival analysis, nodal metastasis and a low AGR remained significant for OS and DFS. Our preliminary study revealed that low preoperative AGR could serve as a valuable and easily-assessed blood-based indicator to predict the prognosis of LSCC patients.
Subject(s)
Carcinoma, Squamous Cell/blood , Carcinoma, Squamous Cell/mortality , Laryngeal Neoplasms/blood , Laryngeal Neoplasms/mortality , Serum Albumin , Serum Globulins , Adult , Aged , Biomarkers, Tumor , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Combined Modality Therapy , Female , Humans , Laryngeal Neoplasms/pathology , Laryngeal Neoplasms/surgery , Male , Middle Aged , Neoplasm Grading , Neoplasm Metastasis , Neoplasm Staging , Preoperative Period , Prognosis , Proportional Hazards Models , ROC CurveABSTRACT
The processing parameters of pump speed, inlet air temperature, outlet air temperature and homogenization pressure were evaluated. Encapsulation efficiency is high with a satisfied releasing rate. Then, acute otitis media (AOM) animal model was built and diet containing orange peel essential oil microcapsules were administrated to AOM animals. Pharmacological test showed that orange peel essential oil treatment could decrease serum and cochlea malondialdehyde (MDA), immunoglobulins A (IgA), immunoglobulins G (IgG), immunoglobulins M (IgM) levels and increase antioxidant enzymes activities. It can be concluded that orange peel essential oil treatment could decrease oxidative injury in acute otitis media rats.
Subject(s)
Citrus sinensis/chemistry , Oils, Volatile/pharmacology , Otitis Media/metabolism , Oxidative Stress/drug effects , Acute Disease , Animals , Capsules , Glutathione/metabolism , Immunoglobulins/metabolism , Male , Malondialdehyde/metabolism , Otitis Media/immunology , Plant Epidermis/chemistry , Rats , Rats, Sprague-DawleyABSTRACT
The present study was to identify and quantitate differentially expressed proteins in laryngeal squamous cell carcinoma (LSCC) tissues with or without lymph node metastasis and to explore transcriptional factors and regulation networks associated with the process. Tissue specimens were taken from 20 patients with LSCC, including 10 cases of LSCC without metastasis LSCC (N0) and 10 cases of LSCC with metastasis LSCC (Nx). Among the 643 unique proteins identified by using iTRAQ labeling and quantitative proteomic technology, 389 proteins showed an abundance change in LSCC (Nx) as compared to LSCC (N0). Cytoskeleton remodeling, cell adhesion, and immune response activation were found to be the main processes in LSCC metastasis. The construction of transcription regulation networks identified key transcription regulators for lymph node metastasis of LSCC, including Sp1, c-myc, and p53, which may affect LSCC metastasis through the epithelial-mesenchymal transition. Furthermore, our results suggest that ubiquitination may be a critical factor in the networks. The present study provides insights into transcriptional factors and regulation networks involved in LSCC metastasis, which may lead to new strategies for treatment of LSCC metastasis.
