Inhibition of 17-DMAG on VEGF expression in transplanted human gastric cancer in nude mice

AIM: To observe the anti-tumor effects of heat shock protein 90(HSP90) inhibitor 17-dimethylaminoethylamino-17 demethoxygeldanamycin (17-DMAG) on the tumor growth and angiogenesis in implanted gastric cancer nude mouse model. METHODS: Human gastric cancer cell HGC-27 was subcutaneous inoculation into the nude mice to develop a tumor model. Ten days later, 24 mice with implanted tumor were randomly divided into 3 groups: 17-DMAG group (receiving 17-DMAG at dose of 25 mg/kg), control group (treated with NS at dose of 10 mL/kg) and 5-fluorouracil(5-FU) group (treated with 5-FU at dose of 20 mg/kg). Four weeks after treatment, the tumor volume and weight, and the inhibitory rates of tumor growth were evaluated. In the meantime, the expression of CD31 was detected by immunohistochemical staining. The expression of vascular endothelial growth factor (VEGF) was determined by Western blotting. RESULTS: The size of xenografts in 17-DMAG treatment group was (288.10±23.32)mm³, and that in 5-FU treatment group was (366.37±26.42)mm³, both were significantly smaller than that in control group (957.66±117.51)mm³. The tumor weight in 17-DMAG treatment group was (0.41±0.02)g, significantly less than that in control group (1.12±0.08)g. The inhibitory rate of 17-DMAG was 63%. A significant decease of MVD in 17-DMAG group (21.72±1.24) was observed as compared to 5-FU group (36.70±1.51) and control group (37.78±1.68). The expression of VEGF in 17-DMAG group (15.39±4.37) was significantly lower than that in 5-FU group (26.11±6.26) and control group (36.45±7.45). CONCLUSION: HSP90 inhibitor 17-DMAG suppresses the expression of VEGF and the angiogenesis of the gastric cancer to inhibit the tumor growth.