RESUMO
OBJECTIVE: The aim of this study was to examine the anti-invasion effect of Shikonin on human high-metastatic adenoid cystic carcinoma (ACC-M) cells and to explain the possible molecular mechanism involved. METHODS: The ACC-M cells were treated with Shikonin (0, 2.5, 5, 10 µM) for 24 h. The protein levels and gelatinolytic activities of MMP-2 and MMP-9 were analyzed using Western blot and Gelatin zymography test, respectively. Matrigel invasion assays were used to investigate tumor invasive potential and electromobility shift assays were used to determine the activity of NF-κB. RESULTS: The invasiveness of ACC-M cells was reduced in a dose dependent manner following 24-h treatment of up to 10 µM of the Shikonin at which concentration no cytotoxicity occurred. The protein levels and gelatinolytic activities of MMP-9 were significantly suppressed by increasing Shikonin concentrations. The down-regulation of MMP-9 appeared to be via the inactivation of NF-κB as the treatment with Shikonin suppressed the protein level of phosphate-IkBa, which was accompanied by a decrease in DNA-binding level of the factor. CONCLUSIONS: Shikonin inhibits tumor invasion via downregulation of MMP-9 expression in ACC-M cells. Pharmacologic inhibition of the NF-κB-mediated MMP-9 expression by Shikonin might be a powerful treatment option for ACC patients in future.
Assuntos
Antineoplásicos/farmacologia , Carcinoma Adenoide Cístico/patologia , Regulação para Baixo , Medicamentos de Ervas Chinesas/farmacologia , Metaloproteinase 9 da Matriz/efeitos dos fármacos , NF-kappa B/efeitos dos fármacos , Naftoquinonas/farmacologia , Antineoplásicos/administração & dosagem , Western Blotting , Carcinoma Adenoide Cístico/fisiopatologia , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Corantes , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Eletroforese em Gel de Poliacrilamida , Humanos , Proteínas I-kappa B/efeitos dos fármacos , Metaloproteinase 2 da Matriz/efeitos dos fármacos , Naftoquinonas/administração & dosagem , Invasividade Neoplásica/patologia , Invasividade Neoplásica/fisiopatologia , Sais de Tetrazólio , Tiazóis , Fatores de Tempo , Fator de Necrose Tumoral alfa/efeitos dos fármacosRESUMO
We report a case of a 64-year-old lady who developed clinical features of Wernicke-Korsakoff syndrome following a laparotomy for small bowel obstruction. Following the operation she developed paralytic ileus and required total parenteral nutrition for one month. A suspected history of average 40 units of weekly alcohol consumption prior to the operation could not be confirmed and the patient did not show any sign of alcohol dependence. Within a few months of treatment with a daily oral dose of thiamine 200 mgs supplemented by multivitamins the patient showed subjective evidence of improvement in confusion, confabulation, and anterograde amnesia, although objective tests showed residual deficits in many areas of cognitive functioning, including immediate and delayed recall of verbal and non-verbal materials, planning and switching of attention.