ABSTRACT
Naringin, a citrus bioflavonoid, has anti-inflammatory actions and cardio- and neuroprotective effects. In addition, naringin exhibits multiple antitumor actions in several cancer types, including osteosarcoma, the most common type of bone cancer. Here, we show that naringin inhibits proliferation and invasion and induces apoptosis in human osteosarcoma cells by inhibiting zinc finger E-box binding homeobox 1 (Zeb1), a transcriptional repressor of epithelial differentiation involved in tumor metastasis. Our expression analyses confirm that Zeb1 is highly expressed in osteosarcoma specimens and cell lines. The effects of naringin, which included downregulation of Cyclin D1, MMP2, and bcl-2, where reproduced by siRNA-mediated Zeb1 silencing, whereas Zeb1 overexpression increased proliferation, migration, and Cyclin D1, MMP2, and bcl-2 levels. In addition, naringin administration reduced tumor nodule formation and attenuated the expression of the above proteins in the livers of mice injected with MG63 osteosarcoma cells. Our study provides preclinical evidence for the potential therapeutic application of naringin in the treatment of osteosarcoma.
Subject(s)
Bone Neoplasms/metabolism , Flavanones/pharmacology , Osteosarcoma/drug therapy , Zinc Finger E-box-Binding Homeobox 1/metabolism , Animals , Apoptosis , Cell Cycle , Cell Movement , Cell Survival , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Male , Mice , Mice, Nude , Neoplasm Invasiveness , Neoplasms, Experimental , Osteosarcoma/metabolism , Young AdultABSTRACT
Osteosarcoma is an aggressive bone tumor primarily affecting children and adolescents. Its cause is not yet fully understood, and there is an urgent need for more effective treatment. In the present study we identified several miRNAs whose expression is altered in osteosarcoma compared to adjacent normal tissue. Moreover, expression levels of one of those miRNAs, miR-506-3p, correlated negatively with expression of RAB3D (a Ras-related protein). Suppression of miR-506-3p in osteosarcoma led to increased expression of RAB3D, which in turn led to increased CDK4 (cyclin-dependent kinase 4) and MMP9 (matrix metalloprotein 9) activities. Our results suggest that miR-506-3p acts as a tumor suppressor in osteosarcoma and that its downregulation leads to tumor cell proliferation and metastasis due to upregulation of RAB3D- and CDK4-mediated signaling. miR-506-3p thus appears be a potentially useful target for adjuvant therapy in osteosarcoma patients.
Subject(s)
Bone Neoplasms/metabolism , MicroRNAs/metabolism , Osteosarcoma/metabolism , rab3 GTP-Binding Proteins/metabolism , Adolescent , Adult , Animals , Bone Neoplasms/pathology , Cell Line , Cell Line, Tumor , Cell Proliferation , Child , Down-Regulation , Female , Gene Expression Regulation, Neoplastic , Gene Silencing , Humans , Male , Mice , Mice, Nude , MicroRNAs/genetics , Neoplasms, Experimental , Osteosarcoma/pathology , Young AdultABSTRACT
Objective To compare the curative effect of arthroscopic transtibial single-bundle posterior cruciate ligament(PCL) reconstruction using LARS artificial ligament and hamstring tendon autograft.Methods Thirty-seven patients who underwent isolated single-bundle PCL reconstruction with remnant preservation technique were evaluated.They were divided into LARS group(n=19) and 4-strand hamstring tendon autograft (4SHG) group (n =18).Minimum follow-up was 2 years.Patients were evaluated preoperatively and postoperatively at the latest follow-up with several parameters,including the international knee documentation committee(IKDC) score,Lysholm knee score,Tegner activity rating and physical examination.Results After operation,in LARS group,Lysholm sorce was 89 (51,100) points,Tegner sorce was 6 (1,9) points,IKDC sorces were normal of 5 cases,nearly normal of 10 cases,abnormal of 3 cases,and obviously abnormal of 1 case,significantly improved compared with before operation (62 (28,98) points,2 (1,5) points,abnormal IKDC score of 8 cases,obviously abnormal of 11 cases;P＜0.001).In 4SHG group,Lysholm sorce was 84(36,100) points,Tegner sorce was 6(1,9) points,IKDC sorces were normal of 5 cases,nearly normal of 9 cases,abnormal of 3 cases,and obviously abnormal of 1 case,better than before operation (64 (28,98) points,2 (1,5) points,IKDC score abnormal of 8 cases,obviously abnormal of 10 cases;P＜0.001).There was significant difference about Lysholm sorce between two groups after operation (P=0.037).The drawer test results show that,after operation,there were 15 case of grade 0,4 cases of grade 1 in LARS group,3 cases of grade 0,11 cases of grade 1,4 cases of grade 2 in 4SHG group,all improved significantly compared with before operation,and the differences were statistically significant(LARS group:x2 =38.000,P＜0.001;4SHG group:x2 =29.143,P＜0.001),and the grade of patients in LARS group were superior to 4SHG group after operation (x2 =15.251,P ＜0.001).Conclusion The clinical effect of using a LARS ligament for PCL reconstruction is more useful than using a 4SHG.
