Effects of Curcumin on in vitro and in vivo Proliferation and Invasion of Osteosarcoma Cells and Its Mechanism Study / 中国药房

ABSTRACT

OBJECTIVE:To investigate the effects of curcumin on proliferation and invasion of osteosarcoma cells and its mechanism. METHODS:In in vitro cell assay,osteosarcoma cells were divided into control group(dimethyl sulfoxide),curcumin low-concentration,medium-concentration and high-concentration groups(10,20,40 μmol/L)and curcumin high-concentration+endogenous miR-21 simulacrum(agomiR-21)group,curcumin high-concentration+agomiR-21 negative control(NC)group. The proliferation(OD value)and invasion ability(transmembrane cells number)of human osteosarcoma cells U-2OS and MG-63 were detected by CCK-8 and Transwell chamber method;the expression of miR-21 and its target gene PDCD4 protein were detected by real-time fluorescence quantitative PCR and Western blot assay. In in vivo cell assay,MG-63 cells were inoculated in mice,and the mice were divided into blank control group(normal saline),curcumin group(20 mg/kg),curcumin+agomiR-21 NC group(20 mg/kg curcumin solution+50 mg/kg agomiR-21 NC solution),curcumin+agomiR-21 group(20 mg/kg curcumin solution+50 mg/kg agomiR-21 solution)with 8 mice in each group;they were given intratumoral injection of relevant medicine once a day,for consecutive 7 d. The volume changes of the tumor were measured within 20 d after medication,and the expression of miR-21 and PDCD4 protein in tumor tissue were detected on 20th day. RESULTS:Compared with control group,the OD value and transmembrane cells number of U-2OS and MG-63 cells were decreased significantly in curcumin low-concentration, medium-concentration and high-concentration groups(P<0.05 or P<0.01);the expression of miR-21 was weakened significantly in curcumin medium-concentration and high-concentration groups of U-2OS and MG-63 cells(P<0.05 or P<0.01),while the expression of PDCD4 protein was strengthened significantly(P<0.01). Compared with curcumin high-concentration+agomiR-21 NC group,the OD value and transmembrane cells number of U-2OS and MG-63 cells were strengthened significantly in curcumin high-concentration+agomiR-21 group(P<0.01). Compared with blank control group,the tumor volume of mice were decreased significantly in curcumin group and curcumin+agomiR-21 NC group(P<0.05 or P<0.01). The expression of miR-21 was decreased significantly in tumor tissue(P<0.01),while the protein expression of PDCD4 was strengthened significantly(P<0.01). Compared with curcumin+agomiR-21 NC group,the tumor volume of mice were increased significantly in curcumin+agomiR-21 group(P<0.05 or P<0.01). The expression of miR-21 in tumor tissue were strengthened significantly(P<0.01),while the expression of PDCD4 protein were weakened significantly(P<0.01). CONCLUSIONS:Curcumin can inhibit the proliferation and invasion of human osteosarcoma cells U-2OS and MG-63,the mechanism of which may be associated with down-regulating the expression of miR-21.