RESUMO
BCL2L10 is an apoptosis-related member of the BCL-2 protein family. The role of BCL2L10 in the pathogenesis of hepatocellular carcinoma (HCC) is poorly understood. This study was aimed to investigate the function and underlying mechanisms of BCL2L10 in HCC. BCL2L10 expression in human HCC and corresponding adjacent normal tissues was investigated by quantitative real-time PCR and Western blot. The biological functions of BCL2L10 in HCC cell lines were determined by cell viability, colony formation, cell apoptosis, cell cycle, and cell metastasis assays, and in vivo by tumorigenicity and lung metastasis assays in nude mice. Human cancer pathway PCR array was employed to explore the genes regulated by BCL2L10 in HCC. BCL2L10 was down-regulated in human HCC tissues compared to their adjacent non-tumor tissues. Ectopic expression of BCL2L10 in HepG2 and Huh7 cells suppressed cell growth as evidenced by cell viability and colony formation assay, and induced cell apoptosis. HCC cells transfected with BCL2L10 revealed an increased cell proportion arrested at G2/M phase, concomitant with a reduction in the cell proportion in S-phase as compared with control cells. Additional, BCL2L10 repressed cell migration and angiogenesis. Over-expression of BCL2L10 also restrained the tumorigenecity and lung metastasis capacity in nude mice. The activation of JAK-STAT3 signaling was suppressed by BCL2L10 in HCC. BCL2L10 was down-regulated in human HCC tissues compared to adjacent normal tissues. BCL2L10 suppressed HCC progression through inhibiting cell growth and metastasis. Thus, BCL2L10 functions as a tumor-suppressor in HCC. © 2016 Wiley Periodicals, Inc.
Assuntos
Carcinoma Hepatocelular/patologia , Regulação para Baixo , Neoplasias Hepáticas/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Nus , Metástase Neoplásica , Transplante de Neoplasias , Transdução de SinaisRESUMO
This study aimed to prepare a poly(propylene fumarate)/(calcium sulphate/beta-tricalcium phosphate) (PPF/(CaSO(4)/beta-TCP)) composite. We first examined the effects of varying the molecular weight of PPF and the N-vinyl pyrrolidinone (NVP) to PPF ratio on the maximum cross-linking temperature and the composite compressive strength and modulus. Then the in vitro biodegradation behaviour of PPF/(CaSO(4)/beta-TCP) composites was investigated. The effects of varying the molecular weight of PPF, the NVP/PPF ratio and the CaSO(4)/beta-TCP molar ratio on the weight loss and the composite compressive strength and modulus were examined. The cross-linking temperature, which increased with increasing molecular weight of PPF and NVP/PPF ratio, ranged from 41 to 43 degrees C for all formulations. The mechanical properties were increased by a decrease in the NVP/PPF ratio. For all formulations, the compressive strength values fell between 12 and 62 MPa, while the compressive modulus values fell between 290 and 1149 MPa. The weight loss decreased either with increasing molecular weight of PPF or with decreasing NVP/PPF ratio and CaSO(4)/beta-TCP molar ratio during degradation. The compressive strength and modulus increased with decreasing NVP/PPF ratio or decreasing CaSO(4)/beta-TCP ratio. The greatest weight loss over 6 weeks was 14.72%. For all formulations, the compressive modulus values fell between 57 and 712 MPa and the compressive strength fell between 0.5 and 21 MPa throughout 6 weeks degradation. Scanning electron microscopy and X-ray diffraction analysis of the PPF/(CaSO(4)/beta-TCP) composites demonstrated that hydroxyapatite was deposited on the surface of CaSO(4)/beta-TCP granules during degradation.