RESUMEN
Tyroserleutide (YSL) is an active, low-molecular-weight polypeptide, comprised of three amino acids, that has shown antitumor effects on human hepatocarcinoma BEL-7402 in vitro and in vivo. In this study, we evaluated the inhibition of YSL on invasion and adhesion of the mouse B16-F10 melanoma cell line by injecting B16-F10 cells into the tail veins of C57BL/6 mice to establish an experimental lung metastasis model. YSL inhibited B16-F10 cell metastasis to lung, reducing the number and area of metastasis lesions. When we treated B16-F10 cells with YSL (0.01, 0.1, 1, 10, or 100 microg/mL) in vitro, we found that YSL inhibited the proliferation of B16-F10 cells with a 28.11% rate of inhibition. YSL significantly decreased the adhesiveness of B16-F10 cells to Matrigel with a 29.15% inhibition rate; YSL also significantly inhibited the invasion of B16-F10 cells, producing an inhibition of 35.31%. By analyses with Western blot and real-time RT-PCR, we found that YSL markedly inhibited the expression of ICAM-1 in B16-F10 cells. These data suggest that YSL inhibits the growth, invasion, and adhesion of B16-F10 cells.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias Pulmonares/secundario , Melanoma Experimental/patología , Oligopéptidos/farmacología , Animales , Western Blotting , Adhesión Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Colágeno/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Evaluación Preclínica de Medicamentos , Femenino , Laminina/metabolismo , Neoplasias Pulmonares/patología , Ratones , Ratones Endogámicos C57BL , Peso Molecular , Invasividad Neoplásica/prevención & control , Trasplante de Neoplasias , Oligopéptidos/química , Proteoglicanos/metabolismo , Distribución Aleatoria , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Trasplante Homólogo , Células Tumorales CultivadasRESUMEN
OBJECTIVE: To investigate the inhibitory effects of tyroservatide and its amino acid mixture on growth of hepatocarcinoma. METHODS: Hepatocarcinoma in nude mice was induced by implantation of cells of human hepatocarcinoma cell line BEL-7402. The inhibition of hepatocarcinoma growth was determined by calculating the tumor volume and measuring the tumor weight. The effects of tyroservatide on tumor cells in nude mice were assessed by immunohistochemical staining of proliferating cell nuclear antigen (PCNA), electron microscopic observation of ultrastructure, and apoptosis of tumor cells using terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL). RESULTS: Tyroservatide significantly inhibited the growth of human hepatocarcinoma in nude mice, with an inhibiting rate more than 60%. But the mixture of amino acid did not show a significant inhibitory effect on the tumor growth. Tyroservatide also induced apoptosis of tumor cells and decreased the expression of PCNA in tumor cells. CONCLUSION: Tyroservatide may significantly inhibit the growth of human hepatocarcinoma in nude mice by inducing apoptosis and inhibiting proliferation of tumor cells.
Asunto(s)
Proliferación Celular/efectos de los fármacos , Neoplasias Hepáticas Experimentales/prevención & control , Neoplasias Hepáticas/prevención & control , Oligopéptidos/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas Experimentales/metabolismo , Neoplasias Hepáticas Experimentales/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Antígeno Nuclear de Célula en Proliferación/metabolismo , Carga TumoralRESUMEN
BACKGROUND & OBJECTIVE: Tripeptide compound tyroservaltide (YSV) has obvious inhibitory effect on experimental liver cancer. This study was to evaluate the inhibitory effect of YSV on the invasion and metastasis of mouse melanoma cell line B16-F10. METHODS: The cytotoxic effect of YSV on B16-F10 cells was assessed by MTT assay, and the effects of YSV on the adhesiveness and invasiveness of B16-F10 cells were determined using Matrigel and a transwell system. B16-F10 cells were injected into the tail veins of C57BL/6 mice to establish an experimental lung metastasis model, and the effect of YSV on lung metastasis was observed. The effect of YSV on the expression of intercellular adhesion molecule-1 (ICAM-1) in lung tissue was detected by immunohistochemistry. RESULTS: YSV (100 microg/ml, 48 h) inhibited the proliferation of B16-F10 cells, with an inhibitory rate of 24.36%; YSV (100 microg/ml, 24 h) inhibited the adhesiveness of B16-F10 cells to Matrigel, with an inhibitory rate of 36.51%; YSV (10 microg/ml, 48 h) inhibited the invasiveness of B16-F10 cells, with an inhibitory rate of 36.53%; YSV [640 microg.(kg.d)-1] inhibited lung metastasis by B16-F10 cells, with an inhibitory rate of 62.21%. The expression of ICAM-1 in lung tissue was lower in YSV group than in normal saline group. CONCLUSION: YSV can inhibit the growth, invasion, and metastasis of B16-F10 cells.