Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 25
Filtrar
1.
Acta Pharmaceutica Sinica ; (12): 89-94, 2019.
Artículo en Chino | WPRIM | ID: wpr-778655

RESUMEN

Liver fibrosis is a tissue repair compensatory response to liver injury caused by various chronic factors, ultimately leading to liver cirrhosis, liver failure and even hepatocellular carcinoma. Abnormal activation of hepatic stellate cells is the cellular basis of liver fibrosis development. Pepstatin Pr, the derivative of pepstatin A, was isolated from Streptomyces sp. CPCC 202950. Our purpose was to investigate the anti-fibrotic activity of pepstatin Pr and explore its molecular mechanism. Hepatic stellate cell LX-2 was stimulated by TGFβ1 and sub- sequently treated with pepstatin Pr. Its cytotoxicity was detected by sulforhodamine B (SRB) assay. The expression of COL1A1, α-SMA and cathepsin D, signaling proteins TGFβ, Smad and YAP/TAZ were detected by Western blot or real-time PCR. The results showed that pepstatin Pr was not cytotoxic to LX-2 cells. And pepstatin Pr significantly reduced the mRNA and protein expression of COL1A1 and α-SMA, which are important liver fibrosis markers. Pepstatin Pr also repressed the protein expression level of cathepsin D, TGFβ1, YAP/TAZ, the phospholation level of Smad2, and YAP nuclear translocation. In conclusion, pepstatin Pr exhibits anti-fibrotic effects in TGFβ1-stimulaed LX-2 cells by mediating YAP-TGFβ-Smad pathway.

2.
Acta Pharmaceutica Sinica ; (12): 1647-1651, 2017.
Artículo en Chino | WPRIM | ID: wpr-779771

RESUMEN

Integrin is a class of important cell surface molecules involved in cell proliferation, differentiation, adhesion and migration processes, which play an important role in a variety of pathological processes. In recent years, with the research in integrin regulation and the treatment of tumor, tissue fibrosis, and other fields, integrin has gradually become a new target in the diagnosis and treatment of diseases. In this article, we provide a summary on the advances of the regulation of integrin gene expression.

3.
Acta Pharmaceutica Sinica ; (12): 189-197, 2017.
Artículo en Chino | WPRIM | ID: wpr-779578

RESUMEN

Bile acids play critical roles in the regulation of metabolism and absorption of lipids. The ileal apical sodium-dependent bile acid transporter (ASBT) located at the enterocyte brush border is responsible for the reuptake of bile acids and the maintenance of bile acid homeostasis. Recently, a number of investigations have been made concerning the regulation and control of ASBT and the relationship between ASBT and intestinal inflammation, tumorigenesis, diabetes mellitus and hyperlipemia, which suggests ASBT as a potential therapeutic target of these diseases. In this review, advances in the study of above-mentioned issues were summarized.

4.
Acta Pharmaceutica Sinica ; (12): 23-2016.
Artículo en Chino | WPRIM | ID: wpr-779129

RESUMEN

Autophagy is a classical regulatory mechanism of energy metabolism and self-update system in the maintenance of the intracellular homeostasis and cell development. Autophagy has been recently found to play a role in tumor development. Autophagy regulates tumor formation, proliferation, metastasis, and metabolism. At the same time, the anticancer drugs formed with autophagic mediators have been used in the treatment, which suggested that improving autophagy activity to inhibit tumor has become a new way for cancer treatment of cancer patients. This article gives an overview of the regulatory mechanism of autophagy, the relationship between autophagy and tumor, and tumor therapy by targeting autophagy.

5.
Acta Pharmaceutica Sinica ; (12): 23-28, 2016.
Artículo en Chino | WPRIM | ID: wpr-320022

RESUMEN

Autophagy is a classical regulatory mechanism of energy metabolism and self-update system in the maintenance of the intracellular homeostasis and cell development. Autophagy has been recently found to play a role in tumor development. Autophagy regulates tumor formation, proliferation, metastasis, and metabolism. At the same time, the anticancer drugs formed with autophagic mediators have been used in the treatment, which suggested that improving autophagy activity to inhibit tumor has become a new way for cancer treatment of cancer patients. This article gives an overview of the regulatory mechanism of autophagy, the relationship between autophagy and tumor, and tumor therapy by targeting autophagy.


Asunto(s)
Humanos , Antineoplásicos , Autofagia , Neoplasias
6.
Acta Pharmaceutica Sinica ; (12): 169-173, 2015.
Artículo en Chino | WPRIM | ID: wpr-251800

RESUMEN

For screening the potential drugs as anti-liver fibrosis candidates, we established a high- throughput drug screening cell model based on COL1A1 promoter. The activity of COL1A1 promoter and luciferase reporter gene can be elevated by TGF-β1, and inhibited by candidate drugs. We constructed a recombined plasmid with COL1A1 promoter and luciferase reporter gene pGL4.17, the activity of COL1A1 promoter was reflected by fluorescence intensity. COL1A1 promoter activity was detected by Dual-Luciferase Reporter Assay System, it came that the relative luciferase activity of COL1A1 promoter was 15.98 times higher than that of control group induced by TGF-β1, showing the recombined plasmid could be used in cell model. The recombined plasmid was transfected into human hepatic stellate cells LX2, detected the effect of potential drugs, and obtained a stable expression system through stable transfection and monoclonal cell culture. A sample which could reduce COL1A1 promoter activity signally by our cell model, decreased collagen I mRNA and protein expression detected by real-time RT-PCR and Western blotting. It indicates this novel cell model can be used in high-throughput drug screening of potential anti-liver fibrosis drugs.


Asunto(s)
Humanos , Colágeno Tipo I , Genética , Evaluación Preclínica de Medicamentos , Métodos , Genes Reporteros , Células Estrelladas Hepáticas , Ensayos Analíticos de Alto Rendimiento , Cirrosis Hepática , Quimioterapia , Luciferasas , Plásmidos , Regiones Promotoras Genéticas , ARN Mensajero , Transfección , Factor de Crecimiento Transformador beta1 , Farmacología
7.
Acta Pharmaceutica Sinica ; (12): 385-392, 2015.
Artículo en Chino | WPRIM | ID: wpr-251767

RESUMEN

Epithelial-mesenchymal transition (EMT) refers to tne transition during which epithelial cells undergo the loss of apical-basal polarity, acquisition of migration capability and transformation into mesenchymal cells. EMT induces breast cancer in situ to developing into metastasis and associates with the drug resistence. The multiple elements including signal pathways, transcriptional factors and downstream genes orchestrate the transition. Among them, the transforming growth factor β (TGF-β) signaling pathway plays a key role in the regulation of EMT in breast cancer. And this paper reviews the development of TGF-β signaling pathway induced EMT in breast cancer.


Asunto(s)
Humanos , Neoplasias de la Mama , Metabolismo , Células Epiteliales , Transición Epitelial-Mesenquimal , Transducción de Señal , Factores de Transcripción , Factor de Crecimiento Transformador beta , Fisiología
8.
Acta Pharmaceutica Sinica ; (12): 1365-1371, 2014.
Artículo en Chino | WPRIM | ID: wpr-299126

RESUMEN

Liver fibrosis is a pathological process of the excessive accumulation of extracellular matrix, especially collagen al (I) in liver. Ultimately, hepatic fibrosis leads to cirrhosis or hepatic failure. Liver fibrosis and early cirrhosis can be reversed, thus control of the development of liver fibrosis is very important for preventive treatment of cirrhosis and hepatic failure. This is a review of potential targets for anti-hepatic fibrosis based on plenty of publications, including TGF-β1 and integrin α(v) and so on, aimed at providing novel therapeutic targets in liver fibrosis.


Asunto(s)
Humanos , Colágeno , Metabolismo , Integrina alfaV , Metabolismo , Hígado , Patología , Cirrosis Hepática , Quimioterapia , Factor de Crecimiento Transformador beta1 , Metabolismo
9.
Acta Pharmaceutica Sinica ; (12): 198-203, 2014.
Artículo en Chino | WPRIM | ID: wpr-297993

RESUMEN

This study aimed to investigate the synergistic effect of lidamycin (LDM) and rituximab on human B cell lymphoma Ramos cells. Cell proliferation was measured using MTS assay, cell apoptosis was analyzed by Annexin V-FITC/PI assay, the expression of apoptosis related proteins was analyzed by Western blotting, and the in vivo lymphoma inhibition was verified using BALB/c mice inoculated via tail vein using Ramos cells which stably expressed pEGFP-N1 plasmid. The results showed that, after the pretreatment with rituximab for 48 h, rituximab and LDM showed significantly synergistic effects on cell proliferation. Cells in combined treatment group had a higher apoptosis rate than that in LDM treatment group. Compared with the LDM treatment group, the expression of apoptosis-related proteins such as Cleaved caspase-3, Cleaved caspase-7, Cleaved caspase-9 and Cleaved PARP in combined treatment groups increased, and expression of cIAP-2 and Bcl-2 decreased. The result of in vivo experiment showed that, in the combined treatment group, the survival time of BALB/c mice was significantly longer than the mice in control group and LDM treatment group, and the degree of tumor accumulation and metastasis to lymph nodes and spleen was lower.


Asunto(s)
Animales , Humanos , Ratones , Aminoglicósidos , Farmacología , Antibióticos Antineoplásicos , Farmacología , Antineoplásicos , Farmacología , Apoptosis , Caspasa 3 , Metabolismo , Caspasa 7 , Metabolismo , Caspasa 9 , Metabolismo , Línea Celular Tumoral , Proliferación Celular , Sinergismo Farmacológico , Enediinos , Farmacología , Proteínas Inhibidoras de la Apoptosis , Metabolismo , Linfoma de Células B , Metabolismo , Patología , Ratones Endogámicos BALB C , Ratones Desnudos , Metástasis de la Neoplasia , Trasplante de Neoplasias , Poli(ADP-Ribosa) Polimerasas , Metabolismo , Proteínas Proto-Oncogénicas c-bcl-2 , Metabolismo , Distribución Aleatoria , Rituximab , Farmacología
10.
Acta Pharmaceutica Sinica ; (12): 204-208, 2014.
Artículo en Chino | WPRIM | ID: wpr-297992

RESUMEN

Sphingosine kinase 1 (SphK1) plays critical roles in cell biological functions. Here we investigated the effects of SphK1 inhibitor SKI II on hepatoma HepG2 cell cycle progression and invasion. Cell survival was determined by SRB assay, cell cycle progression was assayed by flow cytometry, the ability of cell invasion was measured by Matrigel-Transwell assay and protein expression was detected by Western blotting. The results showed that SKI II markedly inhibited HepG2 cell survival in a dose-dependent manner, induced G1 phase arrest in HepG2 cell and inhibited cell invasion. SKI II markedly decreased the expressions of G1-phase-related proteins CDK2, CDK4 and Cdc2 and the levels of cell invasion-associated proteins MMP2 and MMP9. The results showed that SKI II inhibited cell cycle progression and cell invasion, implying SphK1 as a potential target for hepatoma treatment.


Asunto(s)
Humanos , Proteína Quinasa CDC2 , Movimiento Celular , Supervivencia Celular , Quinasa 2 Dependiente de la Ciclina , Metabolismo , Quinasa 4 Dependiente de la Ciclina , Metabolismo , Quinasas Ciclina-Dependientes , Metabolismo , Fase G1 , Células Hep G2 , Metaloproteinasa 2 de la Matriz , Metabolismo , Metaloproteinasa 9 de la Matriz , Metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol) , Tiazoles , Farmacología
11.
Acta Pharmaceutica Sinica ; (12): 1800-1806, 2013.
Artículo en Chino | WPRIM | ID: wpr-298008

RESUMEN

A series of cycloberberine derivatives were designed, synthesized and evaluated for their anti-cancer activities in vitro. Among these analogs, compounds 6c, 6e and 6g showed strong inhibition on human HepG2 cells. They afforded a potent effect against DOX-resistant MCF-7 breast cells as well. The primary mechanism showed that cell cycle was blocked at G2/M phase of HepG2 cells treated with 6g using flow cytometry assay. It significantly inhibited the activity of DNA Top I at the concentration of 0.1 mg mL-1. Our results provided a basis for the development of this kind of compounds as novel anti-cancer agents.


Asunto(s)
Humanos , Antineoplásicos , Química , Farmacología , Berberina , Química , Farmacología , Ciclo Celular , Proliferación Celular , ADN-Topoisomerasas de Tipo I , Metabolismo , Doxorrubicina , Farmacología , Resistencia a Antineoplásicos , Células Hep G2 , Células MCF-7 , Estructura Molecular , Relación Estructura-Actividad
12.
Acta Pharmaceutica Sinica ; (12): 971-978, 2013.
Artículo en Chino | WPRIM | ID: wpr-259521

RESUMEN

Sphingolipids as an important regulator play a critical role in the cell biological functions. Among them, ceramide (Cer) and sphingosine (Sph) induce apoptosis and inhibit cell proliferation; on the contrary sphingosine 1-phosphate (S1P) promotes cell survival and proliferation. The balance between ceramide/sphingosine and S1P forms a so-called "sphingolipid-rheostat", which decides the cell fate. Sphingosine kinases, which catalyze the phosphorylation of sphingosine to S1P, are critical regulators of this balance. Here, we review the role of sphingosine kinase 1 (SphK1) in regulating fundamental biological processes and tumorigenesis and the potential of SphK1 as a new target for cancer therapeutics.


Asunto(s)
Animales , Humanos , Amino Alcoholes , Farmacología , Apoptosis , Movimiento Celular , Proliferación Celular , Ceramidas , Metabolismo , Activación Enzimática , Inhibidores Enzimáticos , Farmacología , Lisofosfolípidos , Metabolismo , Neoplasias , Metabolismo , Patología , Neovascularización Patológica , Fosforilación , Fosfotransferasas (Aceptor de Grupo Alcohol) , Metabolismo , Esfingosina , Metabolismo , Tiazoles , Farmacología
13.
Acta Pharmaceutica Sinica ; (12): 200-205, 2012.
Artículo en Chino | WPRIM | ID: wpr-323058

RESUMEN

A series of novel N-(2-arylethyl) isoquinoline derivatives were designed, synthesized and evaluated for their anti-cancer activities. Among these analogs, compound 9a exhibited the potential anti-cancer activities on HepG2 and HCT116 cells with IC50 values of 2.52 and 1.99 microg x mL(-1), respectively. Cell cycle was blocked at S phase of HepG2 cells treated with 9a by flow cytometry detection. Our results provided a basis for the development of a new series of anti-cancer candidates.


Asunto(s)
Humanos , Antineoplásicos , Química , Farmacología , Ciclo Celular , Proliferación Celular , Células HCT116 , Células Hep G2 , Concentración 50 Inhibidora , Isoquinolinas , Química , Farmacología , Estructura Molecular , Relación Estructura-Actividad
14.
Acta Pharmaceutica Sinica ; (12): 1261-1268, 2012.
Artículo en Chino | WPRIM | ID: wpr-274667

RESUMEN

The use of monoclonal antibodies (mAbs) for cancer therapy has achieved considerable success in recent years. Approximate 17 monoclonal antibodies have been approved as cancer therapeutics since 1997. Antibody-drug conjugates (ADC) are powerful new treatment options for cancer, and naked antibodies have recently achieved remarkable success. The safety and effectiveness of therapeutic mAbs in oncology vary depending on the nature of the target antigen and the mechanisms of tumor cell killing. This review provides a summary of the current state of antibody-based cancer therapy, including the mechanisms of tumor cell killing by antibodies, tumor antigens as antibody targets, clinical effectiveness of antibodies in cancer patients and nanoparticles-based ADCs.


Asunto(s)
Humanos , Anticuerpos Monoclonales , Alergia e Inmunología , Usos Terapéuticos , Antígenos de Neoplasias , Alergia e Inmunología , Antineoplásicos , Usos Terapéuticos , Inmunoconjugados , Usos Terapéuticos , Nanopartículas , Neoplasias , Alergia e Inmunología , Terapéutica
15.
Acta Pharmaceutica Sinica ; (12): 571-575, 2010.
Artículo en Chino | WPRIM | ID: wpr-354589

RESUMEN

To investigate the antitumor activities of the immunoconjugates composed of anti-type IV collagenase monoclonal antibody Fab' fragment and lidamycin (LDM) prepared with different linkers. The immunoconjugates were prepared by linking Fab' to lysine-69 of LDM apoprotein by SPDP, LCSPDP, SMBS or SSMPB as the intermediate drug linkers. Immunoreactivities of the conjugates were determined by ELISA. The cytotoxicities of the conjugates were examined by clonogenic assay. In vivo antitumor effects of the conjugates were evaluated in nude mice bearing subcutaneously implanted HT-1080 tumor. ELISA assay showed that the conjugates retained part of the immunoreactivity of 3G11 against the antigen. The cytotoxicities of the Fab'-SMBS-LDM and Fab'-SSMPB-LDM to HT-1080 cells were significantly potent, compared with Fab'-SPDP-LDM, Fab'-LCSPDP-LDM and free LDM. In animal models at the same condition, free LDM, Fab'-SPDP-LDM and Fab'-LCSPDP-LDM inhibited the growth of HT-1080 tumor by 70.9%, 74.8% and 72.3%, while Fab'-SMBS-LDM and Fab'-SSMPB-LDM reached 78.0% and 87.7%, respectively. The median survival time of the mice treated with free LDM, Fab'-SPDP-LDM and Fab'-LCSPDP-LDM were prolonged by 71.9%, 82.2% and 107.5%, respectively, compared with that of untreated group. Whereas, the median survival time of Fab'-SMBS-LDM and Fab'-SSMPB-LDM were prolonged by 145.2% and 165.8%, respectively, indicating that Fab'-SSMPB-LDM was more effective than Fab'-SMBS-LDM in tumor suppression and life span prolongation. Fab'-SSMPB-LDM has more marked selective antitumor efficacy and lower toxicity, and might be a novel candidate for cancer therapy.


Asunto(s)
Animales , Humanos , Ratones , Aminoglicósidos , Farmacología , Antibióticos Antineoplásicos , Farmacología , Anticuerpos Monoclonales , Alergia e Inmunología , Línea Celular Tumoral , Proliferación Celular , Colagenasas , Alergia e Inmunología , Enediinos , Farmacología , Fibrosarcoma , Patología , Inmunoconjugados , Farmacología , Fragmentos Fab de Inmunoglobulinas , Alergia e Inmunología , Inhibidores de la Metaloproteinasa de la Matriz , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Carga Tumoral
16.
Acta Pharmaceutica Sinica ; (12): 945-951, 2010.
Artículo en Chino | WPRIM | ID: wpr-353400

RESUMEN

G3BP (Ras-GTPase-activating protein SH3 domain binding protein), a protein which binds to RasGAP SH3 domain, belongs to RNA-binding protein family, implicating in the downstream of Ras signaling. G3BP harbors the activities of endoribonuclease and DNA helicase, and can induce stress granules formation. G3BP plays a general role in the signal pathways of cell proliferation, differentiation, apoptosis and RNA metabolism. It has been shown to be over-expressed in a number of human malignancies and has a close relationship with tumor invasion and metastasis. Given that it has been implicated in several pathways that are known to be involved in cancer biology, G3BP may provide a new target for cancer therapy.


Asunto(s)
Animales , Humanos , Proteínas Portadoras , Genética , Metabolismo , ADN Helicasas , Sistemas de Liberación de Medicamentos , Proteínas Activadoras de GTPasa , Usos Terapéuticos , Datos de Secuencia Molecular , Neoplasias , Quimioterapia , Metabolismo , Patología , Fragmentos de Péptidos , Usos Terapéuticos , Fosforilación , Proteínas de Unión a Poli-ADP-Ribosa , ARN Helicasas , Proteínas con Motivos de Reconocimiento de ARN , Transducción de Señal , Proteínas Activadoras de ras GTPasa , Metabolismo , Dominios Homologos src , Genética
17.
Acta Pharmaceutica Sinica ; (12): 219-225, 2009.
Artículo en Chino | WPRIM | ID: wpr-278277

RESUMEN

It has been reviewed that as many as hundreds genes are dysregulated in various kinds of cancers, yet most therapies are targeted toward a single gene. Recently, the mode of cancer treatment has been changed by a shift in thinking from mono-target to multi-target therapies. There is considerable evidence that these have a higher possibility of success than mono-target therapy, and multi-target therapy should remain the most attractive avenue for future treatment strategies. In this article, we attempt to provide evidence for the role of small interfering RNA in multi-target therapy of cancer.


Asunto(s)
Animales , Humanos , Terapia Genética , Neoplasias , Genética , Terapéutica , Interferencia de ARN , ARN Interferente Pequeño , Genética , Usos Terapéuticos , Tolerancia a Radiación
18.
Acta Pharmaceutica Sinica ; (12): 296-302, 2009.
Artículo en Chino | WPRIM | ID: wpr-278267

RESUMEN

In this study, the antitumor activities of VEGF shRNA and tubulin inhibitors on human prostate cancer DU145 cells was investigated, and shRNA transient expression plasmid pCSH1-VEGF targeting VEGF mRNA was constructed. The silence efficiency of pCSH1-VEGF was detected by RT-PCR assay, Western blotting, and Matrigel invasion assay. The sensitivity change of DU145 cells to Taxol and vincristine (VCR) was measured by MTT assay. To detect the effects of pCSH1-VEGF and Taxol in vivo, nude mice model of DU145 xenograft tumor was established by subcutaneous inoculation. The results showed that transcription and expression of VEGF were knocked by pCSH1-VEGF in DU145 cells. Matrigel invasion assay results showed that pCSH1-VEGF significantly reduced the migration of DU145 cells with inhibitory rate of 56.1%. Furthermore, pCSH1-VEGF enhanced the sensitivity of DU145 cells to Taxol and vincristine, and the values of IC50 decreased by 77.3% and 92.6%, respectively. In vivo experiment showed that Taxol, pCSH1-VEGF, combination of pCSH1-VEGF and Taxol inhibited tumor growth by the rates of 48.8%, 56.2% and 81.8%, respectively. The coefficient of drug interaction (CDI) of pCSH1-VEGF and Taxol was 0.82. The data suggested that VEGF shRNA could significantly enhance the sensitivity of human prostate cancer to tubulin inhibitors.


Asunto(s)
Animales , Humanos , Masculino , Ratones , Antineoplásicos Fitogénicos , Farmacología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Vectores Genéticos , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Paclitaxel , Farmacología , Plásmidos , Neoplasias de la Próstata , Metabolismo , Patología , Interferencia de ARN , ARN Interferente Pequeño , Genética , Transfección , Moduladores de Tubulina , Farmacología , Carga Tumoral , Factor A de Crecimiento Endotelial Vascular , Genética , Metabolismo , Vincristina , Farmacología
19.
Biomedical and Environmental Sciences ; (12): 244-252, 2009.
Artículo en Inglés | WPRIM | ID: wpr-360669

RESUMEN

<p><b>OBJECTIVE</b>Lidamycin, an enediyne antibiotic, leads to apoptosis and mitotic cell death of human tumor cells at high and low concentrations. The reason why tumor cells have distinct responses to lidamycin remains elusive. This study was to elucidate if cellular prosurvival molecules are involved in these responses.</p><p><b>METHODS</b>Cleavage of chromatin and DNA was observed by chromatin condensation and agarose gel electrophoresis. Accumulation of rhodamine 123 in lidamycin-treated cells was assayed by flow cytometry. Cell multinucleation was detected by staining with Hoechst 33342. Western blot and senescence-associated beta-galactosidase (SA-beta-gal) staining were used to analyze protein expression and senescence-like phenotype, respectively.</p><p><b>RESULTS</b>SIRT1 deacetylase remained unchanged in 0.5 nmol/L lidamycin whereas cleavage occurred when apoptosis was induced by lidamycin. Increased FOXO3a, SOD-1 and SOD-2 expression and transient phosphorylation of ERK were detected after exposure of human hepatoma BEL-7402 cells to 0.5 nmol/L lidamycin. High expressions of SIRT1 and Akt were found in colon carcinoma HCT116 p53 knock-out cells exposed to lidamycin. Degradation of PARP and p53 by lidamycin as a substitute for SIRT1 and Akt was confirmed with caspase inhibitor Q-VD-OPh and proteasome inhibitor MG132. Resistance to lidamycin-induced DNA cleavage was observed in breast cancer doxorubicin-resistant MCF-7 cells. This was not induced by P-glycoprotein as no accumulation of rhodamine 123 was detected in the resistant cells following exposure to lidamycin. In contrast to sensitive MCF-7 cells, a lower multinucleation rate for the resistant cells was measured following exposure to equal concentrations of lidamycin.</p><p><b>CONCLUSIONS</b>Cellular prosurvival molecules, such as SIRT1, Akt, SOD-1, SOD-2 and other unknown factors can influence the action of lidamycin on human tumor cells.</p>


Asunto(s)
Humanos , Aminoglicósidos , Farmacología , Antibióticos Antineoplásicos , Farmacología , Muerte Celular , Línea Celular Tumoral , División del ADN , Doxorrubicina , Farmacología , Enediinos , Farmacología , Proteína Forkhead Box O3 , Factores de Transcripción Forkhead , Genética , Metabolismo , Regulación de la Expresión Génica , Quinasas de Proteína Quinasa Activadas por Mitógenos , Genética , Metabolismo , Poli(ADP-Ribosa) Polimerasas , Genética , Metabolismo , Proteínas Proto-Oncogénicas c-akt , Genética , Metabolismo , Transducción de Señal , Sirtuina 1 , Sirtuinas , Genética , Metabolismo , Proteína p53 Supresora de Tumor , Genética , Metabolismo
20.
Acta Pharmaceutica Sinica ; (12): 704-709, 2007.
Artículo en Chino | WPRIM | ID: wpr-268592

RESUMEN

This study is to investigate the antitumor activities of the immunoconjugates composed of anti-type IV collagenase monoclonal antibody 3G11 and lidamycin (LDM) prepared by different methods. The immunoconjugates were prepared by linking 2-iminothiolane modified 3G11 to lysine-69 of LDM apoprotein by SPDP and SMBS as the intermediate drug linker. Immunoreactivity of the conjugates was determined by ELISA. The cytotoxicity of the conjugates was examined by clonogenic assay. Antitumor effects of the conjugates in vivo were evaluated in nude mice bearing subcutaneously implanted HT-1080 tumor. ELISA assay showed that the immunoconjugates retained the immunoreactivity of 3G11 against type IV collagenase. The cytotoxicity of the 3G11-SMBS-LDM to HT-1080 cells was significantly more potent than that of free LDM and 3G11-SPDP-LDM. In animal model at the same condition, free LDM inhibited the growth of HT-1080 tumor by 71.2%, while 3G11-SPDP-LDM and 3Gl1-SMBS-LDM reached 77.1% and 86.1%, respectively. The median survival time of the mice treated with free LDM was prolonged by 71.9% compared with that of untreated group. Whereas, the median survival time of 3G11-SPDP-LDM and 3G11-SMBS-LDM was prolonged by 125.3% and 163.7%, respectively, indicating that 3G11-SMBS-LDM was more effective than 3G11-SPDP-LDM in tumor suppression and life span prolongation. 3Gll-SMBS-LDM has more selective antitumor efficacy and lower toxicity, and might be a novel candidate for cancer therapy. LDM was more effective than 3G11-SPDP-LDM in tumor suppression and life span prolongation. 3Gll-SMBS-LDM has more selective antitumor efficacy and lower toxicity, and might be a novel candidate for cancer therapy.


Asunto(s)
Animales , Humanos , Ratones , Aminoglicósidos , Usos Terapéuticos , Antibióticos Antineoplásicos , Usos Terapéuticos , Anticuerpos Monoclonales , Alergia e Inmunología , Línea Celular Tumoral , Proliferación Celular , Colagenasas , Alergia e Inmunología , Enediinos , Usos Terapéuticos , Fibrosarcoma , Patología , Terapéutica , Inmunoconjugados , Usos Terapéuticos , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Carga Tumoral
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA