The Experiment Study Of FMJX For Injection On Anti-tumor Effect

Objective: Fumagillin that excreted by Aspergillus Fumigatus washydrolyzed by alkali to produce Fumagillol. The FMJX was obtained byreconstructing the structure of Fumagillol. The anti-tumor, anti-metastasisand anti-angiogenesis effect and mechanism of FMJX was investigated.The anti-tumor and anti-metastasis effect and mechanism of FMJX wasinvestigated in bearing tumor mouse model with H22, B16 and Lewis andthe anti-angiogenesis effect of FMJX was investigated in ChorioallantoicMembrane Assay (CAM) model.Methods:1. H22, B16 and Lewis were inoculated to the right groin of KM orC57/BL mice. Sixty mice were randomly divided into six groups:control group treated with normal saline;solvent group treated withvehicle, FMJX group treated with three different concentrations (15,30,60mg/kg) and CTX group treated with CTX(30mg/kg). From thesecond day, drugs were given through ip. every other day for 10 times.2. B16 and Lewis cells were suspended in normal saline and injectedinto the skin of claw of crus C57/BL mice. Sixty mice were randomlydivided into six groups: control group treated with normal saline;solventgroup treated with vehicle, FMJX group treated with three differentconcentrations (15 , 30 , 60mg/kg) and CTX group treated withCTX(30mg/kg). From the second day, drugs were given through ip. everyother day for 17 times. After 3 weeks, the crus of C57/BL mice were cutand calculate the inhibitiion rate. Mice were sacrificed on 35th days afterinjection and the lung was taken and put in Bouin's. Optical microscopewas used to observe the tumor metastasis to the lung.3. CMC carriors containing different dose of FMJX(0,5μg,10μg,25μg) were implanted on top of CAM when chick embryos developed onday 6, vessels which towards carrior were counted after 48h.Results:1. Anti-tumor experiment in vivo ① In bearing tumor mouse modelof H22, the tumor weights of control group, solvent group, FMJX group(15, 30, 60mg/kg) and CTX group (30mg/kg) were(2.29±0.80)g,(2.14±0.91)g, (1.54±0.59)g,(1.24±0.86)g, (0.86±0.27)g and (0.81±0.36)grespectively. The average inhibition rate (IR) was 3.76%, 41.84%, 54.40%,72.85% and 75.69% respectively. ② In bearing tumor mouse model of B16,the tumor weights of control group, solvent group, FMJX group (15, 30,60mg/kg) and CTX group (30mg/kg) were (3.62±0.73)g, (3.69±0.97)g,(1.96±1.10)g, (1.85±1.69)g, (1.13±0.87)g and (1.04±0.58)g respectively.The average inhibition rate (IR) was 1.31%, 38.19%, 50.00%, 62.62% and70.46% respectively.③ In bearing tumor mouse model of Lewis, thetumor weights of control group, solvent group, FMJX group(15,30,60mg/kg) and CTX group (30mg/kg) were (3.30±1.10)g,(3.24±1.46)g, (2.21±1.78)g, (1.96±1.51)g, (1.06±1.95)g and (0.90±0.50)grespectively. The average inhibition rate (IR) was 2.83%, 33.00%, 45.40%,63.23% and 71.70% respectively.2. Anti-metastasis Experiment ① In tumor metastasis model of B16,the tubercles in lung of control group, solvent group, FMJX group (15,30, 60mg/kg) and CTX group (30mg/kg) were 8.75, 8.64, 5.17, 4.44, and4.10 (P<0.05,0.01) .② In tumor metastasis model of Lewis, the tuberclesin lung of control group, solvent group, FMJX group (15, 30, 60mg/kg)and CTX group (30mg/kg) were 11.31, 11.07, 6.54, 4.58, and 4.18(P<0.05,0.01).3. In CAM model, numbers of vessles at carrior-CAM boundary weresignificantly different to control (P<0.05,0.01). The inhibition rate ofcontrol, FMJX(0,5μg,10μg,25μg) was 4.38%, 59.64%,67.92% and96.67%.FMJX exerts great efficacy of anti-angiogenesis, which can inhibitangiogenesis on CAM model in low concentration.Conclusion:The results of those studies show that FMJX has the effect ofanti-tumor, anti-metastasis and the side-effect is mild. We think that themechanisms of anti-tumor and anti-metastasis have concern with the effectof restraining angiogenesis.