The inhibitory effects of 3TSR combined with 5-fluorouracil on gastric cancer

Abstract

Objective To investigate the anti-tumor efticacy of angiogenic inhibitor three thrombospondin-1 type 1 repeats (3TSR) combined with 5-fluorouracil (5-Fu) on gastric cancer.Methods SGC-7901 cells were inoculated subcutaneously into 24 BALB/C mice,and the mice were divided into four groups:control group,3TSR group (3TSR 3 mg/kg every day,i.p.),5-Fu group (5-Fu 24 mg/kg,twice every week,i.p.) and 3TSR plus 5-Fu group (3TSR 3 mg/kg every day,and 5-Fu 24 mg/kg,twice every week,i.p.) with 6 mice each group.After treatment for three weeks,the mice were sacrificed.The tumor volume,microvessel index,cancer cell apoptosis and expression of matrix metalloproteinase (MMP)-2 was analyzed,consecutively.Results Tumor volume,as compared with control group,was reduced dramatically in 3TSR,5-Fu and 3TSR plus 5-Fu groups by 39.2%,43.7% and 63.2%,respectively.The microvessel number and average microvessel density in 3TSR,5-Fu and 3TSR plus 5-Fu groups were ( 10.9 ±3.6) and (739.3±121.6) μm2,(42.9±8.6)and (1503.3 ±202.4) μm2,(20.9 ±4.3) and (833.3±76.9)μm2,respectively.Microvessel index in 3TSR group and 3TSR plus 5-Fu group was significantly lower than in 5-Fu group ( P＜0.05 ).The apoptosis rate of cancer cells in 3TSR,5-Fu and 3TSR plus 5-Fu groups was (3.1 ± 1.0) %,( 12.7 ± 3.6) %,and ( 11.9 ± 4.0) %,respectively,with the difference being not significant between 3TSR and control groups,but that in 5-Fu and 3TSR plus 5-Fu groups was significantly higher than in 3TSR and control groups ( P＜0.05 ).The positive expression rate of MMP-2 in control,3TSR,5-Fu and 3TSR plus 5-Fu groups was (4.2 ± 1.3)%,(4.6 ± 1.2)%,(3.8 ± 2.0)% and (4.9 ± 1.6)%,respectively,with the difference being not significant among four groups (P ＞ 0.05).Conclusion 3TSR inhibits tumor angiogenesis,remarkably reduces tumor volume and average microvessel and increases tumor necrosis.The antiangiongenesis effects of 3TSR were not related with MMP-2 expression.3TSR showed synergistic effects in combination of 3TSR and 5-Fu. Key words: Gastric tumor; Angiogenesis; 5-Fu