RESUMO
Chemotherapy resistance is the main reason for the failure of cancer treatment. The mechanism of drug resistance is complex and diverse. In recent years, the role of glucose metabolism and mitochondrial function in cancer resistance has gathered considerable interest. The increase in metabolic plasticity of cancer cells' mitochondria and adaptive changes to the mitochondrial function are some of the mechanisms through which cancer cells resist chemotherapy. As a key molecule regulating the mitochondrial function and glucose metabolism, PGC-1α plays an indispensable role in cancer progression. However, the role of PGC-1α in chemotherapy resistance remains controversial. Here, we discuss the role of PGC-1α in glucose metabolism and mitochondrial function and present a comprehensive overview of PGC-1α in chemotherapy resistance.
Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias , Humanos , Glucose/metabolismo , Mitocôndrias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismoRESUMO
OBJECTIVES: This diet-controlled study was designed to examine effects of konjac glucomannan (KGM) supplement on the bowel habits and colonic ecology in 7 constipated subjects. In addition, the mechanisms by which KGM modulated the bowel habit were explored. METHODS: Seven constipated subjects who passed bowel movement less than once a day participated in this diet-controlled linear study that consisted of a 21-d placebo period, a 7-d adaptation period, and a 21-d KGM-supplemented (1.5 g, tid) period. The large bowel response and fecal characteristics were recorded daily. Stools were collected individually on days 15-21 of placebo and KGM periods for analyses of colonic ecology indices such as fecal microflora, pH and short chain fatty acid content. Fecal component was determined to illustrate the fermentation of KGM. RESULTS: KGM supplement slightly but significantly increased the weekly defecation frequency from 4.1 +/- 0.6 to 5.3 +/- 0.6 and slightly eased the bowel movement. The fecal wet weight (g/d) and percent moisture were not significantly altered with the fiber supplement. However, the dry fecal weight (g/d) was increased mainly in the soluble mass. KGM supplement increased the fecal concentration (log counts/g wet feces) of lactobacilli, and the daily output (log counts/d) of bifidobacteria, lactobacilli and total bacteria in this diet-controlled study. In addition, fermentation of KGM resulted in greater fecal acetate, propionate and i-butyrate concentrations and lower fecal pH. CONCLUSION: The modest dose of KGM supplement promoted bowel movement by 30% and improved colonic ecology in constipated adults.
Assuntos
Catárticos/farmacologia , Colo/microbiologia , Constipação Intestinal/tratamento farmacológico , Defecação/efeitos dos fármacos , Ácidos Graxos Voláteis/biossíntese , Mananas/farmacologia , Adulto , Bactérias Anaeróbias/crescimento & desenvolvimento , Bactérias Anaeróbias/metabolismo , Bifidobacterium/crescimento & desenvolvimento , Bifidobacterium/metabolismo , Contagem de Colônia Microbiana , Estudos Cross-Over , Fibras na Dieta/administração & dosagem , Suplementos Nutricionais , Fezes/química , Fezes/microbiologia , Feminino , Fermentação , Humanos , Concentração de Íons de Hidrogênio , Lactobacillus/crescimento & desenvolvimento , Lactobacillus/metabolismo , Probióticos , Método Simples-CegoRESUMO
OBJECTIVE: Konjac glucomannan (KGM) has been shown to relieve constipation, which could be associated with increased stool bulk and improved colonic ecology. METHODS: This placebo-controlled study consisted of a 21-d placebo period, a 7-d adaptation period when volunteers consumed KGM progressively, and a 21-d KGM-supplemented period (1.5 g/meal, 4.5 g/d). Eight healthy adults consumed 7-d cycle menus of typical low-fiber Chinese food throughout the study. The gastrointestinal response was monitored daily. Stools were fully collected on days 15 to 21 of placebo and KGM periods to determine the fecal mass, components, microflora, and short-chain fatty acid contents. RESULTS: The KGM supplement significantly increased the mean defecation frequency (number/day), wet stool weight, and dry stool weight (g/d) by approximately 27.0% (P < 0.05), 30.2% (P < 0.05), and 21.7% (P < 0.05), respectively. The dry fecal mass increased mainly in the plant and soluble material, whereas bacterial mass tended to increase from 12.9 +/- 1.6 to 13.6 +/- 2.7 g/d (P > 0.05). However, KGM significantly promoted the fecal concentrations (log counts/g wet feces) of lactobacilli (P < 0.05) and total bacteria (P < 0.05), and promoted the daily output (log counts per day) of bifidobacteria (P < 0.05), lactobacilli (P < 0.05), and total bacteria (P < 0.05) as evaluated by the fluorescence in situ hybridization method. KGM supplement also promoted colonic fermentation as shown in the decreased fecal pH (P < 0.05) and increased fecal short-chain fatty acid concentrations (P < 0.05). CONCLUSION: Supplementation of KGM into a low-fiber diet promoted the defecation frequency in healthy adults, possibly by increasing the stool bulk, thus promoting the growth of lactic acid bacteria and colonic fermentation.