RESUMO
Liver cancer is the fifth most frequently diagnosed type of cancer in men worldwide. Recombinant human programmed cell death 5 (rhPDCD5) has been shown to enter a variety of cells by clathrin-independent endocytosis. Tissue specimens from 32 hepatocellular carcinoma (HCC) patients were collected for analysis of PDCD5 expression using ELISA. It was confirmed that the preoperative serum levels of PDCD5 protein in patients with HCC were significantly lower than the postoperative serum levels. Moreover, the serum PDCD5 levels were significantly correlated with portal invasion and lymph node metastasis. rhPDCD5 inhibited cell proliferation as indicated by an MTT assay, and induced apoptosis and S-phase arrest in HCC cells as demonstrated by flow cytometric analysis. Furthermore, rhPDCD5 suppressed tumor growth in established xenograft tumor models. In addition, Pitstop2 was used to block clathrin-dependent endocytosis (CDE), which confirmed that the antitumor effect of rhPDCD5 in HCC cells is mediated via CDE.
Assuntos
Antineoplásicos/farmacologia , Proteínas Reguladoras de Apoptose/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Endocitose/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Proteínas de Neoplasias/farmacologia , Proteínas Recombinantes de Fusão/farmacologia , Animais , Antineoplásicos/química , Proteínas Reguladoras de Apoptose/sangue , Proteínas Reguladoras de Apoptose/química , Proteínas Reguladoras de Apoptose/genética , Carcinoma Hepatocelular/patologia , Feminino , Engenharia Genética , Humanos , Neoplasias Hepáticas/patologia , Masculino , Camundongos Endogâmicos NOD , Camundongos SCID , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/química , Proteínas de Neoplasias/genética , Sulfonamidas/farmacologia , Tiazolidinas/farmacologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Liver cancer in men is the fifth most frequently diagnosed cancer worldwide. Human Krüppel-like factor (KLF9) gene, localized on human chromosome 9q13, has been implicated in mediating a diverse range of biological processes including stem cell maintenance and differentiation of T- and B-lymphocytes. In this study, we confirmed that the levels of KLF9 mRNA and protein were lower in hepatocellular carcinoma (HCC) tissue compared to normal tissue. In addition, we confirmed that upregulation of KLF9 inhibited cell proliferation and mobility and induce apoptosis in HepG2 cells depending on programmed cell death protein 5 (PDCD5) expression. However, no interaction was found between KLF9 and PDCD5 using fluorescence resonance energy transfer (FRET) and co-immunoprecipitation (co-IP). We confirmed that PDCD5 overexpression stimulated the promoter activities of KLF9 by luciferase reporter assays.
Assuntos
Proteínas Reguladoras de Apoptose/biossíntese , Carcinoma Hepatocelular/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Neoplasias Hepáticas/genética , Proteínas de Neoplasias/biossíntese , Apoptose/genética , Proteínas Reguladoras de Apoptose/genética , Linfócitos B/metabolismo , Linfócitos B/patologia , Carcinoma Hepatocelular/patologia , Diferenciação Celular , Proliferação de Células , Cromossomos Humanos Par 9 , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/patologia , Proteínas de Neoplasias/genética , Regiões Promotoras Genéticas , RNA Mensageiro , Linfócitos T/metabolismo , Linfócitos T/patologiaRESUMO
Liver cancer in men is the fifth most frequently diagnosed cancer worldwide. Programmed cell death 5 (PDCD5) is an apoptosis related gene and plays an important role in the pathogenesis and development of cancer. In this study, we confirmed that the levels of PDCD5 mRNA and protein were lower in hepatocellular carcinoma (HCC) tissue compared to normal tissue. PDCD5 expression was significantly associated with HBV infection, tumor number, lymph node metastasis and the survival time of the patients with HCC. In addition, the serum levels of PDCD5 and AFP in the patients were significantly positively correlated. We also confirmed that upregulation of PDCD5 was able to inhibit cell proliferation and mobility, induce apoptosis and G1 arrest. Interestingly, PDCD5 also inhibited proteasome activity similarly to the proteosome inhibitor MG132. PDCD5 could be considered as a reliable marker of favorable prognosis of HCC patients.
