Objective      To investigate the inhibitory effect of Norrin on apoptosis of gastric cancer cells.       Methods      The expression of Norrin was detected in 151 gastric cancer tissues with different histological grades by immunohistochemistry

followed by clinic pathological feature analysis. The expression of Norrin in different gastric cell lines was evaluated by Western blot analysis. Gastric cancer cell line BGC823 with low expression of Norrin was constructed by RNA interference using shRNA plasmid. Western blot  analysis was applied to confirm the effect of Norrin knockdown. Cell apoptosis in the Norrin normal-expression group (Lv-sh-ctrl group) and Norrin low-expression group (Lv-sh-Norrin group) was detected by flow cytometry. Finally

Western blot analysis was used to detect the expressions of apoptosis promoting proteins (Bax and cleaved Caspase-3)

and apoptosis inhibiting proteins (Mcl-1 and Bcl-2).       Results      The expression of Norrin in the gastric tumor tissues was significantly higher than that in the para-tumor tissues. The expression of Norrin was associated with Lauren classification

histological grade

TNM stage and survival rate (P0.05)

rather than the gender

age

location

tumor size and histological diagnosis (P0.05). Norrin was highly expressed in poorly differentiated BGC823 cells

but lowly expressed in well or moderately differentiated SGC7901 cells and AGS cells. The apoptotic rate of gastric cancer cells was significantly increased by Norrin knockdown. The apoptosis rate [(12.26±0.70)%] of the Lv-sh-Norrin group was higher than that [(7.58±0.68)%] of the Lv-sh-ctrl group (P0.05). Western blot analysis showed that Mcl-1 protein and Bcl-2 protein were down-regulated in the Lv-sh-Norrin group

while Bax protein and cleaved Caspase-3 were up-regulated.       Conclusion      Norrin inhibits the apoptosis of gastric cancer cells through down-regulation of Bax and cleaved caspase-3 and up-regulation of Mcl-1 and Bcl-2.