Antitumor Effects Of IL‐21 And Combination With 5‐Fu On Human Gastric Cancer Cell And Its Mechanism

Objective: To evaluate the effects and mechanism of cell proliferation, migration potentiality and apoptosis on human gastric cancer cell SGC-7901 induced by IL-21 and combination with 5-Fu. Methods:(1)SGC-7901 cells were cultured.SGC-7901 cells were treated with different groups :the group IL-21(IL-21 100ng/ml),the group 1/2 5-Fu+IL-21(5-Fu 25μg/ml+IL-21 100ng/ml),the group 5-Fu(5-Fu 50μg/ml),the group 5-Fu+IL-21(5-Fu 50μg/ml+IL-21 100ng/ml),for 24 h, 48 h, respectively. The inhibitory rate of cell proliferation was detected by MTT assay.(2)Scratching test was taken to evaluate the migration potentiality of gastric cancer cells with different treatments.(3) The expression of the caspase-3,caspase-8, bcl-2 and c-myc protein in human gastric cancer cell treated with different groups by Western Blot assay.Results:(1)Compared with the group 5-Fu,inhibitory effect of the group IL-21 and 1/2 5-Fu+IL-21 were markedly lower at 24 h and 48 h,but at 48 h,there were significant differences between the group 5-Fu and 1/2 5-Fu+IL-21(p>0.05).The combination of IL-21 and 5-Fu showed an markedly higher inhibitory effect than the group 5-Fu both 24 h and 48h(p<0.001).(2)The scratching test showed that all of the four groups made a very significant inhibitory effect on the migration potentiality of SGC-7901 cells. At 24 h and 48 h, migration distances of the group IL-21 and 1/2 5-Fu+IL-21 were shorter than the group 5-Fu(p<0.001). The migration distances between the group 5-Fu+IL-21 and the group 5-Fu showed marked differences(p<0.001).(3)TUNEL test showed that the group IL-21, 1/2 5-Fu+IL-21, 5-Fu and 5-Fu+IL-21 made a very significant cell apoptosis effect on SGC-7901 cells, and the effects gradually decreased. The apoptosis rate between the group 5-Fu+IL-21 and the group 5-Fu showed marked differences. Compared with the group 5-Fu, the group 1/2 5-Fu+IL-21 made a markedly lower cell apoptosis effect at 24 h,but the differences were smaller at 48 h.(4)Western Bloting analysis showed that the expression of caspase-3, caspase-8 and c-myc of the group 5-Fu+IL-21 were significantly higher than the group 5-Fu, and the expression of bcl-2 was lower than the group 5-Fu(p<0.001). Conclusion(1) IL-21 can inhibit proliferation and migration of SGC-7901 cell, and induce apoptosis of SGC-7901 cell.(2)IL-21 combined with 5-Fu can significantly enhance effects of proliferation,migration and apoptosis on SGC-7901.(3) IL-21 combined with half-dose 5-Fu still can induce cell proliferation,but effects of migration and apoptosis were lower than 5-Fu. IL-21 combined with half-dose 5-Fu still has a meaning of alleviating adverse reactions by chemotherapy drugs.(4)The mechanism that IL-21 combined with can induce cell proliferation, migration and apoptosis may be caused by c-myc, bcl-2,. caspase-3 and caspase-8.