Anti-metastasis effect of curcumin on human pancreatic cancer

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. Key words: Pancreatic neoplasms; Neoplasm metastasis; Cucurmin