Antimetastatic effects of cordycepin and its molecular mechanism in human hepatoma MHCC97H cells in vitro and in vivo / 药学学报

ABSTRACT

The objective of this study was to examine the antimetastatic effects of cordycepin and elucidate its molecular mechanism using MHCC97H cells in vitro and in vivo. Cellular proliferation was detected with MTT assay. The migration and metastatic potential were measured with scratch wound healing as well as transwell migration assays in vitro. Protein expression was detected by Western blotting. Antitumor and antimetastatic effects of cordycepin were evaluated by subcutaneous xenograft and lung metastatic model in vivo. The results demonstrated that cordycepin significantly inhibited MHCC97H cells proliferation and metastasis which was due to the down-regulation of AKT, p-AKT, p-GSK-3β, β-catenin, N-cadherin, MMP-7, MMP-9 and up-regulation the expression of E-cadherin. Furthermore, cordycepin inhibited tumor growth and metastasis in a dose-dependent manner in vivo. Cordycepin(40 and 20 mg·kg-1)and 5-fluorouracil group significantly inhibited the tumor weights to 0.38 ± 0.04, 0.61 ± 0.08 and 0.65 ± 0.07 g, respectively, comparing with the control group(1.52 ± 0.46 g)(P < 0.01), but not 10 mg·kg-1 cordycepin group(1.13 ± 0.36 g)(P > 0.05); the lung metastasis nodus numbers showed the same results, which in all group above(48.9 ± 7.2, 67.2 ± 9.4, 73.6 ± 8.6, respectively)were fewer than the control group(123.5 ± 14.5)(P < 0.01), except 10 mg·kg-1 cordycepin(106.4 ± 11.3)(P > 0.05). Collectively, cordycepin inhibited MHCC97H cell proliferation and metastasis in vivo and in vitro.