RESUMEN
This study tested the hypothesis that heparanase (HPSE) is related to tumor metastasis and curcumin (CCM) inhibits tumor metastasis by down-regulating HPSE expression. MTT, Transwell assays, and RT-PCR were used to study the effects of CCM on the migration and invasion of CT26 cells and the expression of HPSE. CT26 cells were transfected with lentivirus to establish HPSE-overexpressing cells (OE) and corresponding negative control cells (NC). Signal pathways involved in down-regulating the expression of HPSE and inhibiting the migration and invasion of CT26 cells by CCM were screened by the liquid crystal chip. HPSE promoted CT26 cells migration and invasion, and CCM inhibited the proliferation and metastasis of CT26 cells. The results of RT-PCR indicated that CCM down-regulated HPSE expression. Liquid phase microarray showed that CCM inhibited the phosphorylation of P38 and STAT5 in CT26 cells and NC cells. In contrast, the inhibitory function of CCM was markedly enhanced when HPSE was overexpressed (P < 0.05). In short, HPSE is closely related to metastasis of colon cancer cells. CCM inhibits colon cancer cell migration and invasion by inhibiting HPSE expression, which may be related to P38 MAPK and JAK/STAT5 signal pathways.
Asunto(s)
Neoplasias del Colon/inmunología , Curcumina/farmacología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glucuronidasa/inmunología , Proteínas de Neoplasias/inmunología , Línea Celular Tumoral , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Regulación Enzimológica de la Expresión Génica/inmunología , Regulación Neoplásica de la Expresión Génica/inmunología , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/inmunología , Metástasis de la NeoplasiaRESUMEN
Immunosuppression may occur for a number of reasons related to an individual's frailty, debility, disease or from therapeutic iatrogenic intervention or misadventure. A large percentage of morbidity and mortality in immunodeficient populations is related to an inadequate response to infectious agents with slow response to antibiotics, enhancements of antibiotic resistance in populations, and markedly increased prevalence of acute inflammatory response, septic and infection related death. Given known relationships between intracellular calcium ion concentrations and cytotoxicity and cellular death, we looked at currently available data linking blockade of calcium ion channels and potential decrease in expression of sepsis among immunosuppressed patients. Notable are relationships between calcium, calcium channel, vitamin D mechanisms associated with sepsis and demonstration of antibiotic-resistant pathogens that may utilize channels sensitive to calcium channel blocker. We note that sepsis shock syndrome represents loss of regulation of inflammatory response to infection and that vitamin D, parathyroid hormone, fibroblast growth factor, and klotho interact with sepsis defense mechanisms in which movement of calcium and phosphorus are part of the process. Given these observations we consider that further investigation of the effect of relatively inexpensive calcium channel blockade agents of infections in immunosuppressed populations might be worthwhile.
Asunto(s)
Bloqueadores de los Canales de Calcio/uso terapéutico , Canales de Calcio/inmunología , Enfermedades Transmisibles/tratamiento farmacológico , Huésped Inmunocomprometido , Sepsis/tratamiento farmacológico , Calcio/inmunología , Calcio/metabolismo , Canales de Calcio/genética , Enfermedades Transmisibles/genética , Enfermedades Transmisibles/inmunología , Enfermedades Transmisibles/mortalidad , Farmacorresistencia Microbiana/genética , Factores de Crecimiento de Fibroblastos/genética , Factores de Crecimiento de Fibroblastos/inmunología , Regulación de la Expresión Génica , Glucuronidasa/genética , Glucuronidasa/inmunología , Humanos , Proteínas Klotho , Hormona Paratiroidea/genética , Hormona Paratiroidea/inmunología , Fósforo/inmunología , Fósforo/metabolismo , Riesgo , Sepsis/genética , Sepsis/inmunología , Sepsis/mortalidad , Análisis de Supervivencia , Vitamina D/inmunología , Vitamina D/metabolismoRESUMEN
Astragalus membranaceus (AM), a traditional Chinese medicinal herb, has immunoregulatory properties in many diseases. We investigated the effects and mechanism of Astragalus membranaceus extract (AME) in the macrophage migration and immune response mediator release. The viability of Ana-1 macrophages treated with AME was evaluated by the MTT method. The secretion and mRNA levels of IL-1ß and TNF-a were measured by ELISA and RT-PCR, respectively. Macrophage migration was assayed by transwell assay. The activity of heparanase (HPA) was determined by a heparin-degrading enzyme assay. Our results didn't show any toxicity of AME in macrophages. AME increased the activity of HPA, cell migration, mRNA levels and secretion of IL-1ß and TNF-a in macrophages. Pretreatment with anti-HPA antibody reduced cell migration, secretion of IL-1ß and TNF-a did not change the mRNA levels of IL-1ß and TNF-a significantly in AME-treated macrophages. This suggests that AME may increase the release of immune response mediator and cell migration via HPA to activate immune response in macrophages.