ABSTRACT
Objective To explore the expression of a new candidate tumor suppressor N-myc downstream regulated gene 2 (NDRG2) in bladder cancer tissues and to investigate its clinical and pathological significance.Methods Formalin-fixed,paraffin-embedded tissue sections from 62 cases of bladder carcinomas and 10 cases of normal bladder tissues were analyzed retrospectively with immunohistochemistry (S-P method).Results The NDRG2 gene was highly expressed in normal bladder tissues,but low expressed in bladder carcinoma tissues.Positive expression of NDRG2 was detected in 8 of the 10 (80.0％) normal tissues and 40.3％ in bladder carcinoma ones (x2 =3.98,P ＜0.05).Furthermore,with the degree of malignancy increased,the positive expression of NDRG2 in bladder carcinoma samples was decreased.The expression of NDRG2 in bladder carcinoma was negatively correlated(r =-0.288,P ＜0.05) with C-myc(r =-0.436,P ＜0.01) and positively correlated with p53 in bladder carcinoma tissues(r =0.717,P ＜0.01).Conclusions The level of NDRG2 expression was lower in bladder carcinomas than in normal tissues.NDRG2 may play an important role in bladder carcinogenesis and in the progress of bladder cancers.
ABSTRACT
Objective To investigate the antitumor activities of adenovirus-mediated NDRG2 gene (Ad-NDRG2) and docetaxel on human prostate cancer DU145 cells.Methods The protein expressions of cyclin D1,cycliu E,and NDRG2 in the cells were determined by Western blot.MTT and flow cytometry were used to observe the effects of docetaxel (10-6 mol/L,10-7 mol/L,and 10-s mol/L) and Ad-NDRG2 on prostate cancer cell line DU145 in single or synergistic administration ways for 24 and 48 hours in vitro.Male BALB/C-nu mice with DU145 prostate cancer cell lines were treated by docetaxel and Ad-NDRG2 singly or synergistically in vivo.Results After infected by adenovirus,the protein expression of NDRG2 increased,but cyclin D1 and cyclin E decreased in DU145 cells.Ad-NDRG2 inhibited the cell growth (inhibition ratio =41.8％,t =4.18,P ＜0.01),promoted apoptosis (apoptosis ratio =32.4％,x2 =11.66,P ＜0.05),changed the ratio of G2/M phase from 50.2％ to 23.6％,and reversed partially the G2/M arrest,of DU145 cells induced by 10-7 mol/L docetaxel.In vivo experiment showed that docetaxel,Ad-NDRG2,and combination of docetaxel and Ad-NDRG2 inhibited tumor growth with a inhibition rate of 30.7％,28.2％,and 55.8％,respectively.The coefficient of drug interaction (CDI) of docetaxel and Ad-NDRG2 was 0.89.Conclusions Ad-NDRG2 can enhance the growth suppression and apoptosis induced by docetaxel in synergistic way in vitro and in vivo.It demonstrated the great potential of Ad-NDRG2 in the treatment of androgen-independent prostate carcinoma.
ABSTRACT
Objective To observe the expression change of HRG-1 gene between urinary bladder carcinoma and normal tissues,and to investigate the effect of HRG-1-siRNA on the proliferation and apoptosis of human bladder carcinoma cells.Methods Immunohistochemisty was used to detect the expression of HRG-1 in 85 cases of bladder carcinomas and 20 normal bladder tissues.The siRNA of HRG-1 was designed,synthesized,and transfected into bladder cancer cell line T24.Results The HRG-1 gene expression had significant differences between bladder carcinoma and normal bladder tissues (P ＜ 0.05).The positive expression of HRG-1 gene had significant differences between the pathological grades and clinical stages of bladder carcinomas (P ＜0.05).After treated with siRNA,the expression levels of HRG-1 protein and mRNA in T24 cells decreased obviously (P ＜ 0.05).The apoptosis rate of T24 cells transfected with HRG-1-siRNA was significantly different from control-siRNA group and blank group (P ＜ 0.01).Conclusions The high expression of HRG-1 gene may play an important role in bladder carcinoma,and siRNA targeting HRG-1 can suppress HRG-1 protein expression markedly and enhance apoptosis of T24 cells.