AIM:To investigate the effects and mechanism of d-limoneneon the growth and metastasis of gastric cancer in vivo.METHODS:Metastatic model simulating human gastriccancer was established by orthotopic implantation ofhistologically intact human tumor tissue into gastric wallof nude mice.One percent d-limonene was orallyadministered at dose of 15 ml/kg every/other day for sevenweeks.Eight weeks after implantation,tumor weight,inhibition rate,apoptotic index(AI),microvessel density(MVD),vascular endothelial growth factor(VEGF),variationof ultrastructure,and the presence of metastasis wereevaluated,respectively,after the mice were sacrificed.RESULTS:The tumor weight was significantly reduced in5-FU group(2.55±0.28 g),d-limonene group(1.49±0.09 g)and combined treatment group(1.48±0.21 g)comparedwith the control group(2.73±0.23 g,P<0.05).In 5-FUgroup,d-limonene group,combined treatment group,theinhibition rates were 2.60%,47.58% and 46.84% and 0,respectively; AI was(3.31±0.33)%,(8.26±1.21)%,(20.99±1.84)% and(19.34±2.19)%,respectively;MVD was(8.64±2.81),(16.77±1.39),(5.32±4.26)and(5.86±2.27),respectively;VEGF expression was(45.77±4.79),(41.34±5.41),(29.71±8.92)and(28.24±8.55),respectively.Theincidences of peritoneal metastasis also decreasedsignificantly in 5-FU group(77.8%),d-limonene group(20.0%)and combined group(22.2%)compared withcontrol group(100%)versus 62.5%,30% and 22.2%)(P<0.05).Liver metastasis was also inhibited and theincidences decreased significantly in 5-FU group,d-limonene group and combined group than that in controlgroup(87.5% vs 55.5%,20.0% and 22.2% respectively)(P<0.05).The incidence of ascites in control group,5-FUgroup,d-limonene group and combined group was 25.0%,22.2%,0,0,respectively and 12.5%,11.1% 0,0,withrespect to the metastasis rate to other organs.CONCLUSION:d-limonene has antiangiogenic andproapoptotic effects on gastric cancer,thereby inhibitstumor growth and metastasis.Combination of d-limonenewith cytotoxic agents may be more effective. AIM: To investigate the effects and mechanism of d-limoneneon the growth and metastasis of gastric cancer in vivo. METHODS: Metastatic model simulating human gastric cancer was established by orthotopic implantation ofhistologically intact human tumor tissue into gastric wall of nude mice. One percent d-limonene was orally administered at a dose of 15 ml / kg every other day for seven weeks. After weeks after implantation, the tumor weight, inhibition rate, apoptotic index (AI), microvessel density (MVD), vascular endothelial growth factor and the presence of metastasis wereevaluated, respectively, after the mice were sacrificed .RESULTS: The tumor weight was significantly reduced in5-FU group (2.55 ± 0.28 g), d-limonene group (1.49 ± 0.09 g) and combined treatment group ± 0.21 g) compared with the control group (2.73 ± 0.23 g, P <0.05) .In 5-FUgroup, d-limonene group, combined treatment group, the rates were 2.60%, 47.58% and 46.84% and 0, respectively; AI was (3.31 ± 0.33)%, (8.26 ± 1.2 (20.99 ± 1.84)% and (19.34 ± 2.19)%, respectively; MVD was (8.64 ± 2.81), (16.77 ± 1.39), (5.32 ± 4.26) and (5.86 ± 2.27) were (45.77 ± 4.79), (41.34 ± 5.41), (29.71 ± 8.92) and (28.24 ± 8.55), respectively. These margins of peritoneal metastasis also decreased in slightly 5-FU group (77.8%) and d- limonene group ) and combined group (22.2%) compared withcontrol group (100%) versus 62.5%, 30% and 22.2%) (P <0.05) .Liver metastasis was also inhibited and theincidences decreased significantly in 5-FU group, d-limonene group and the combined group than that in control group (87.5% vs 55.5%, 20.0% and 22.2% respectively) (P <0.05). The incidence of ascites in control group, 5-FUgroup, d-limonene group and combined group was 25.0% 22.2%, 0,0, respectively and 12.5%, 11.1% 0,0, withrespect to the metastasis rate to other organs.CONCLUSION: d-limonene has antiangiogenic andproapoptotic effects on gastric cancer, thereby inhibit tumor growth and metastasis. Combine of d- limonenewith cytotoxic agents may be m ore effective.