OBJECTIVETo study the association between single nucleotide polymorphisms of thioredoxin reductase-2 (TrxR2) gene and the susceptibility to Kashin-Beck disease (KBD).

METHODSPolymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to analyze the genotype frequencies of rs5748469 in TrxR2 gene in 84 KBD patients and 109 healthy control subjects.

RESULTSThe genotype frequencies of A/A, A/C, and C/C in the KBD patients were 83.33%, 15.48% and 1.19%, as compared with the frequencies of 74.31%, 25.69%, and 0.00% in the healthy control, respectively, showing no significant difference in the single nucleotide polymorphisms of TrxR2 gene between the two groups (P=0.13).

CONCLUSIONNo obvious correlation can be found between rs5748469 polymorphisms in TrxR2 gene and the susceptibility to KBD.

Adult ; Alleles ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Kashin-Beck Disease ; genetics ; Male ; Middle Aged ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Thioredoxin Reductase 2 ; genetics

OBJECTIVEThis study examined whether the two polymorphisms of GPX1 (198Pro--> Leu) and TXNRD2 (370Lys-->Arg) contributed alone or in combination, to the risk of gastric cancer development.

METHODSA total of 361 patients with gastric cancer and 363 cancer-free controls were recruited and their genotypes of the two polymorphisms were determined by polymerase chain reaction-based restrictive fragment length polymorphism (PCR-RFLP) method. Odds ratio (OR) and 95% confidence interval (CI) were computed using unconditional logistic regression model.

RESULTSGPX1 and TXNRD2 polymorphisms individually were not associated with the risk of gastric cancer. Gene-gene interaction of GPX1 and TXNRD2 polymorphisms decreased the risk of gastric cancer. Carrying the protective genotype might decrease the risk at 62% (OR = 0.38, 95% CI = 0.26-0.55, P < 0.001) as compared with the risk genotype.

CONCLUSIONThe GPX1 198 Pro/Pro and TXNRD2 370Arg/Arg genotypes might be associated with the genetic susceptibility of gastric cancer.

Alleles ; Case-Control Studies ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Glutathione Peroxidase ; genetics ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Stomach Neoplasms ; genetics ; Thioredoxin Reductase 2 ; genetics

OBJECTIVETo explore the effect of nuclear factor erythroid-2 related factor 2 (Nrf2) and thioredoxin reductase (TrxR) gene on proliferation of chronic myeloid leukemia (CML) line cells and its mechanism.

METHODSFour interfering sequences of Nrf2 and one negative control sequence were designed and synthesised based on the principle of target sequence of siRNA, then constructed lentivirus vectors, which were transfected into K562 cell lines. The transfection effect was observed by laser scanning confocal microscope (LSCM) and flow cytometer (FCM); The depressing effect of siRNA was analyzed by real-time PCR. The cell proliferation inhibiting rate was measured with CCK-8 assay, the apoptotic rate by Annexin V-PE/PI with FCM and the apoptotic morphology of cells by LSCM.

RESULTSThe transfection efficiency of lentivirus was 65%. One cell line K562-C3 which significantly inhibited Nrf2 mRNA was obtained by real-time PCR, Nrf2 relative quantitation (RQ) expressions were 1.003±0.093 and 0.344±0.032 in the control group and K562-C3 respectively; TrxR expression also decreased with RQ as 1.090±0.549 and 0.395±0.029 respectively. The cellular proliferation inhibition rates of K562-C3 were (4.74±0.39)%, (6.13±1.78)% and (25.36±3.77)%, respectively at 24, 48 and 72 h. The apoptotic rate induced by K562-C3 (29.9%) at 72 hours was obviously higher than in the control group (7.9%). The Annexin V-PE positive K562-C3 cells presented the following apoptotic characteristics, such as karyopyknosis, nuclear fragmentation and apoptotic bodies observed by LSCM.

CONCLUSIONNrf2 specific siRNA could repress its expression at the cellular level and down-regulate the expression of its downstream antioxidant enzyme, such as TrxR, which lead to increased apoptotic rate and decreased cell proliferation.

Apoptosis ; Cell Proliferation ; Down-Regulation ; Genetic Vectors ; Humans ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; metabolism ; pathology ; NF-E2-Related Factor 2 ; metabolism ; RNA, Messenger ; genetics ; RNA, Small Interfering ; genetics ; Thioredoxin-Disulfide Reductase ; metabolism

Human thioredoxin reductase (TrxR) system is associated with cancer cell growth and anti-apoptosis process. Effects of 1,2-[bis(1,2-benzisoselenazolone-3(2H)-ketone)]ethane (BBSKE), a novel TrxR inhibitor, were investigated on human leukemia cell lines HL-60 and K562. BBSKE treatment induced cell growth inhibition and apoptosis in both cell lines. Apoptosis induced by BBSKE is through Bcl-2/Bax and caspase-3 pathways. Ehrlich's ascites carcinoma-bearing mice were used to investigate the anti-tumor effect of BBSKE in vivo. Tumor-bearing mice treated with BBSKE showed an increase of life span with a comparable effect to cyclophosphamide (CTX). These results suggest a potential usage of BBSKE as a therapeutic agent against non-solid tumors.
Apoptosis ; drug effects ; Bridged Bicyclo Compounds, Heterocyclic ; pharmacology ; Cell Proliferation ; drug effects ; Enzyme Inhibitors ; pharmacology ; HL-60 Cells ; Humans ; K562 Cells ; Organoselenium Compounds ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; physiology ; Thioredoxin-Disulfide Reductase ; antagonists & inhibitors ; bcl-2-Associated X Protein ; physiology