Anti-metastasis effect of curcumin on human pancreatic cancer / 中华胰腺病杂志

ABSTRACT

Objective To investigate whether curcumin could inhibit the metastasis of pancreatic cancer in vitro and in vivo and its mechanism.Methods Pancreatic cancer AsPC-1 cells were treated with different concentrations of curcumin.After 72 hours,cell survival rate were detected by MTT and the appropriate concentration of curcumin was selected.After treated with 6 μmol/L curcumin,early apoptosis of AsPC-1 cells were detected by Annexin V-FITC/PI double staining flow cytometry,and the effects of curcumin on the migration and invasion of AsPC-1 cells were observed.After establishment of the orthotopic nude mouse model of pancreatic cancer,the mice were orally treated with low dose (20 mg/kg body weight) and high dose (40 mg/kg body weight) of curcumin respectively.Eight weeks later mice were sacrificed to observe the tumor metastasis,immunohistochemical methods were used to detect the positive expressions of CD34,NF-κB and MMP-9 in the tumor tissue.Results Curcumin of different concentrations could inhibit the proliferation of AsPC-1 cells and induce its apoptosis in a dose dependent manner,and 6.μmol/L was the best dose of curcumin.After 6 μmol/L curcumin treatment,the migration coverage of AsPC-1 decreased from 70％ to 10％,the number of penetrating cells decreased from 136/200x magnification to 17/200x magnification,and the difference between the two groups was statistically significant (P ＜0.05).In the nude mouse model of pancreatic cancer,the size of the tumor decreased from (97.8 ± 15.3) mm3 to (44.3 ± 9.7) mm3 in high dose group and (28.1 ±7.1)mm3 in low dose group,the number of distant metastasis decreased from 108.3 ±6.7 to 29.5 ±4.5 and 8.9 ± 2.4,the expression of CD34 decreased from 20.5 ± 2.3 to 10.3 ± 1.2 and 7.9 ± 3.2,and the expression of MMP-9 decreased from 85.2 ± 2.3 to 53.2 ± 1.2 and 34.2 ± 3.1,and the difference was statistically significant (P ＜ 0.05).Conclusions Curcumin can inhibit the metastasis of pancreatic cancer both in vitro and in vivo,and its effect may be related to the inhibition of expressions of CD34 and MMP-9.