RESUMEN
Cellular movement is mainly orchestrated by actin-dependent cytoskeleton in which Rho GTPase Rac1 or vasodilator-stimulated phosphoprotein (VASP) closely collaborates. In the present in vitro study, we investigated the inhibitory effect and underlying molecular mechanism of icariin, a pure extract of the traditional Chinese medicine Herba epimedii, on the invasive and migration properties of human gastric cancer cell line BGC-823. At 50% growth-inhibiting concentration, icariin significantly suppressed tumor cells migration and invasion, which were traceable to down-regulation of Rac1 and VASP. Together with icariin, the selected siRNA targeting Rac1 or VASP reinforced these inhibitory effects. Rac1-siRNA-dependent down-regulation of Rac1 led to a large drop in VASP expression, whereas VASP-siRNA led to a slight fall in Rac1 expression, implying that the amount of Rac1 may influence VASP expression level. Moreover, transfection with Rac1 plasmids pcDNA3-EGFP-Rac1-Q61L led to the enhancement in expression level of both Rac1 and VASP. These results indicate that icariin exerts negative effects on tumor cell invasion and migration via the Rac1-dependent VASP pathway and may be a potential anti-cancer drug.
Asunto(s)
Moléculas de Adhesión Celular/metabolismo , Movimiento Celular/efectos de los fármacos , Flavonoides/farmacología , Proteínas de Microfilamentos/metabolismo , Fosfoproteínas/metabolismo , Transducción de Señal/efectos de los fármacos , Neoplasias Gástricas/patología , Proteína de Unión al GTP rac1/metabolismo , Moléculas de Adhesión Celular/deficiencia , Moléculas de Adhesión Celular/genética , Línea Celular Tumoral , Humanos , Concentración 50 Inhibidora , Proteínas de Microfilamentos/deficiencia , Proteínas de Microfilamentos/genética , Invasividad Neoplásica , Fosfoproteínas/deficiencia , Fosfoproteínas/genética , Plásmidos/genética , ARN Interferente Pequeño/genética , Proteína de Unión al GTP rac1/deficiencia , Proteína de Unión al GTP rac1/genéticaRESUMEN
OBJECTIVE: To detect the in vitro effect of the traditional Chinese medicine on the tachyzoites of Toxoplasma gondii. METHODS: Supernatant (1.5 ml) of different doses of the traditional Chinese medicine (Changqing capsule) was collected by normal saline immersion and 2.5 x 10(4) Toxoplasma gondii tachyzoites were added in each paste well for 8 hours. Spiramycin, pyrimethamine and azithromycin in different doses were used as controls. Normal saline was used as negative control. Mice were inoculated with drug-treated tachyzoites intraperitoneally or intragastrically. The normal mice were subcultured after 8 days for 3 generations. RESULTS: The incident number of the infected mice was significantly different among groups with different drugs and doses: 2/60, 16/60, 10/60 and 10/60 in the groups of Changqing capsule, spiramycin, pyrimethamine and azithromycin respectively (P < 0.05). No mice were found incident in groups of high and medium dose Changqing capsule while 2 out of 20 found sick in the low dose group (P < 0.05). The subculture observation showed that 2 and 1 mice in the first generation of the low dose Changqing capsule group inoculated intraperitonelly and intragastrically were found infected respectively. 2 mice of the second generation in low dose spiramycin group and 1 mouse of the third generation in low dose pyrimethamine group were also found infected. CONCLUSION: The in vitro killing effect of the Changqing capsule on the tachyzoites of Toxoplasma gondii is better than the current clinical drugs and shows a positive correlation with the dosages.