RESUMEN
Glycolysis is a typical conduit for energy metabolism in pancreatic cancer (PC) due to the hypoxic microenviroment. Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate and is considered to be a key checkpoint of anaerobic glycolysis. The aim of the present study was to explore the mechanism of interactions between hypoxia, HIF-1/2α and LDHA, and the function of LDHA on PC cells by analyzing 244 PC and paratumor specimens. It was found that LDHA was over-expressed and related to tumor stages. The result of in vitro study demonstrated that hypoxia induced LDHA expression. To explore the relationship between HIF and LDHA, chromatin immunoprecipitation assay and luciferase assay were performed. The result showed that HIF-1/2α bound to LDHA at 89bp under the hypoxic condition. Furthermore, knockdown of endogenous HIF-1α and HIF-2α decreased the LDHA expression even in the hypoxic condition, which was accompanied with a significant decrease in lactate production and glucose utilization (p < 0.01). Immunofluorescence in the 244 specimens showed that HIF-1/2α was over-expressed and associated with LDHA over-expression (p < 0.0001). Forced expression of LDHA promoted the growth and migration of PC cells, while knocking down the expression of LDHA inhibited the cell growth and migration markedly. In summary, the present study proved that HIF1/2α could activate LDHA expression in human PC cells, and high expression of LDHA promoted the growth and migration of PC cells.
Asunto(s)
Hipoxia de la Célula/fisiología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Neoplasias Pancreáticas/metabolismo , Línea Celular Tumoral , Progresión de la Enfermedad , Femenino , Humanos , Isoenzimas/metabolismo , Lactato Deshidrogenasa 5 , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/enzimología , Neoplasias Pancreáticas/patologíaRESUMEN
Two non-destructive instrumental methods, infrared spectroscopy (IR) and X-ray diffraction (XRD), were studied for quality evaluation of Lobelia chinensis Lour. (L. chinensis). We obtained the IR spectra and XRD patterns of L. chinensis collected from different sources. The similarity of samples was analyzed by calculating the cosine coefficient. The cosine values were in the range of 0.83-0.90, indicating that the main components of L. chinensis samples are similar. Sample L1 and L6 showed a slightly lower similarity than that of L2, L3, L4, L5 detected by the two methods, which revealed that IR and XRD methods exhibited analogous detection ability for quality evaluation of L. chinensis. The two methods could be highly recommended as simple and rapid detection means for quality evaluation of L. chinensis.