ABSTRACT
Ring1 and YY1 binding protein (RYBP), a new member of the polycomb group protein family, has been reported to play an important role in various biological processes. Recently, more and more studies have demonstrated an implication of RYBP in cancer development. However, the specific role of RYBP in anaplastic thyroid cancer (ATC) remains unknown. In this study, we investigated for the first time the expression pattern and biological functions of RYBP in ATC. We showed that RYBP was lowly expressed in ATC tissues and cell lines. We also found that overexpression of RYBP inhibited ATC cell proliferation, invasion, and cisplatin resistance. Furthermore, we observed that upregulation of RYBP decreased the phosphorylation of EGFR and ERK1/2 in ATC cells. Taken together, our data indicated that RYBP might be considered as a promising therapeutic target for the treatment of ATC.
Subject(s)
Cell Proliferation/drug effects , Cisplatin/pharmacology , Drug Resistance, Neoplasm/drug effects , Intracellular Signaling Peptides and Proteins/biosynthesis , Neoplasm Proteins/biosynthesis , Thyroid Carcinoma, Anaplastic , Thyroid Neoplasms , Cell Line, Tumor , Cell Proliferation/genetics , Drug Resistance, Neoplasm/genetics , Humans , Intracellular Signaling Peptides and Proteins/genetics , MAP Kinase Signaling System/drug effects , MAP Kinase Signaling System/genetics , Neoplasm Invasiveness , Neoplasm Proteins/genetics , Repressor Proteins , Thyroid Carcinoma, Anaplastic/drug therapy , Thyroid Carcinoma, Anaplastic/genetics , Thyroid Carcinoma, Anaplastic/metabolism , Thyroid Carcinoma, Anaplastic/pathology , Thyroid Neoplasms/drug therapy , Thyroid Neoplasms/genetics , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/pathologyABSTRACT
BACKGROUND AND OBJECTIVES: Protein-calorie malnutrition (PCM) is one of the most suffered complications in cancer patients. Polyphyllin I (PPI), a saponin isolated from rhizome of Paris polyphylla, is a potential candidate in cancer therapy. In this study, the influence of nutritional status on the absorption of PPI in rats was explored after oral administration. METHODS: PCM rats, namely mal-nourished (MN) rats, were induced from well-nourished (WN) rats by caloric restriction protocol. Intestinal absorption of PPI in WN and MN rats was evaluated by pharmacokinetic and intestinal perfusion methods. The potential mechanisms between two groups were investigated on the basis of intestinal permeability, intestinal efflux and PPI's depletions in vivo. The intestinal permeability was analyzed by determining the concentration of paracellular marker transport in serum and the expression of junction proteins in intestine. The intestinal efflux was evaluated through comparing the protein level of P-glycoprotein (P-gp) in intestine, and the depletions of PPI and/or generation of its metabolites in liver and intestines were analyzed by liquid chromatography triple quadrupole mass spectrometry (LC-MS/MS) method. RESULTS: Compared to WN rats, the oral systemic exposure of PPI was significantly increased in MN rats, evidenced by significant enhancement of maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC0-60h) by more than 2.51- and 3.71-folds as well as terminal elimination half-life (t1/2) prolonged from to 7.3 to 14.1 h. Further studies revealed that the potential mechanism might be associated with combined contribution of improved intestinal absorption and depressed deglycosylation of PPI in MN rats. Furthermore, enhanced intestinal absorption of PPI was benefited from increased intestinal permeability and decreased intestinal efflux in MN rats. Meanwhile, the former manifested as increased transport of paracellular marker and decreased junction proteins levels, while the later evidenced by reduced P-gp expression. CONCLUSIONS: The oral exposure of PPI was enhanced in MN rats, which suggested that nutritional status alters the absorption of PPI, and thus the dosage of PPI should be modified during the treatment of cancer patient with PCM.
Subject(s)
Antineoplastic Agents, Phytogenic/metabolism , Diosgenin/analogs & derivatives , Intestinal Absorption , Intestine, Small/metabolism , Liliaceae , Nutritional Status , Protein-Energy Malnutrition/metabolism , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Administration, Oral , Animal Nutritional Physiological Phenomena , Animals , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacokinetics , Biotransformation , Diosgenin/administration & dosage , Diosgenin/isolation & purification , Diosgenin/metabolism , Diosgenin/pharmacokinetics , Disease Models, Animal , Intestine, Small/physiopathology , Liliaceae/chemistry , Liver/metabolism , Male , Models, Biological , Permeability , Protein-Energy Malnutrition/physiopathology , Rats, Sprague-Dawley , Rhizome , Tight Junctions/metabolismABSTRACT
Objective To investigate the effect of obestatin on the apoptosis of rat pancreatic islet cell line INS1 induced by high glucose .Methods INS1 cells were cultured in different concentrations of glucose .The survival rate and proliferation of INS1 cells were detected by MTT method;Hoechst33258 nuclear staining was used to de-tect nuclear morphology.caspase-3 method was used to study the relationship between the protective effect of obestatin and the PI3K pathway;Finally,using real-time PCR detection of FOXO1 and SREBP1c, Bax, PDX-1 expression, to further clarify the protective effect of obestatin on cells.Results In high glucose condition,obesta-tin promoted the proliferation of INS1 cells at 100 nmol/L,and promoted the proliferation of INS 1 cells significantly ( P<0.01 , compared with the control group and high glucose group ) .Obestatin can reduce high glucose-induced apoptosis(P<0.01).The expressions of FOXO1,SREBP1c,Bax and PDX-1 decreased,while the expression of FOXO1,SREBP1c,Bax and PDX-1 increased in high glucose group .Conclusions OB can attenuate the injury of INS1 cells induced by high glucose in rats .
