RESUMEN
Liver cancer, also known as primary liver cancer, is cancer that starts in the liver. JNU-144, a new meroterpenoid purified from Lithospermum erythrorhizon, has exhibited promising anticancer activity; however, the molecular mechanisms of action of JNU-144 on malignant cells remain unclear. Our studies revealed that JNU-144 suppressed cell viability and proliferation in hepatoma cells by downregulating mTOR activation. Meanwhile, JNU-144 activated the intrinsic apoptosis pathway and subsequently triggered apoptotic cell death in SMMC-7721 cells. We also found that JNU-144 inhibited the epithelial-mesenchymal transition in both SMMC-7721 and HepG2 cells through reprogramming of epithelial-mesenchymal transition (EMT)-related gene expression or regulating protein instability. These findings indicate that JNU-144 exerts potent anticancer activity in hepatoma cells and may be developed as a potential therapeutic drug.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Transición Epitelial-Mesenquimal/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/tratamiento farmacológico , Serina-Treonina Quinasas TOR/genética , Terpenos/farmacología , Antígenos CD/genética , Antígenos CD/metabolismo , Antineoplásicos Fitogénicos/aislamiento & purificación , Cadherinas/genética , Cadherinas/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/genética , Humanos , Lithospermum/química , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Extractos Vegetales/química , Transducción de Señal , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/metabolismo , Terpenos/aislamiento & purificación , Carga Tumoral/efectos de los fármacos , Vimentina/genética , Vimentina/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo , beta Catenina/genética , beta Catenina/metabolismoRESUMEN
OBJECTIVE: To study the pathologic characteristics of bone marrow for CD5 positive small B cell lymphoma (SBL).â© METHODS: The pathologic profiles of 92 patients with CD5 positive SBL were retrospectively analyzed. The morphologic and immunophenotypic features were analyzed by flow cytometry and immunohistochemistry. IgH/CCND1 was examined by fluorescence in situ hybridization (FISH).â© RESULTS: A total of 92 patients with CD5 positive SBL were enrolled in this study, including 56 (60.9%) chronic lymphocytic leukemia /small lymphocytic lymphoma (CLL/SLL), 23 (25.0%) mantle cell lymphoma (MCL) and 13 other SBL (14.1%). Among the 13 other cases, 5, 4 and 4 cases were follicular lymphoma (FL), lymphoplasmacytic lymphoma (LPL) and splenic marginal zone lymphoma (SMZL), respectively. The frequency of patterns for bone marrow infiltration was as follow: diffuse pattern (19/92), mixed pattern (15/92), nodular pattern (9/92), interstitial pattern (8/92), and intrasinusodial pattern (2/92). All patients expressed CD19, CD20 and CD5. According to the immunophenotypic score system, all the CLL patients had 4-5 scores, while SMCL and other SBL patients had less than 3 scores. For the other SBL patients, 5 FL expressed CD10, while 3 FL, 1 LPL and 3 SMZL expressed CD23. There was a significant difference in the expression of CD23, sIgM, FMC7, CD11C and CD22 between the CLL and MCL groups (P<0.01). All 23 MCL patients expressed cyclin D1 and showed IgH/CCND1 gene translocation by FISH detection.â© CONCLUSION: CD5 positive SBL includes a variety of types of lymphoma. Patterns of bone marrow for CD5 positive SBL are diversity. Immunophenotypic analysis by flow cytometry is essential in the diagnosis and differential diagnosis of CD5 positive SBL, especially for CLL.