Effects and mechanism of Lanthanum Citrate on proliferation and apoptosis of human hepatocellular carcinoma cell line SMMC-7721 / 中华肝胆外科杂志

ABSTRACT

Objective To investigate the effect and the possible mechanism of Lanthanum Citrate on the proliferation and apoptosis of human hepatocellular carcinoma cell line SMMC-7721 through the Hedgehog signaling pathway.Methods Hhsignaling pathway inhibitor KAAD-cyclopamine and Lanthanum Citrate in different concentrations were used to treat human hepatocellular carcinoma cell line SMMC-7721.Cell proliferation was detected by MTT method.The apoptosis rate was detected by Annexin V/PI flow cytometry.The expressions of the regulative genes,such as CyclinD1,p21,Caspase-3,Bcl-2,Gli1,Shh were detected by Western blot.The mRNA expressions of Gli1 and Shh were detected by q-PCR.Results In control group,SMMC-7721 cells were treated with 0.1 mmol/L Lanthanum Citrate group,and 15 μnol/L KAAD-cyclopamine for 48 h,and expression of CyclinD1 protein in each group was (1.41 ± 0.21),(0.71 ±0.08) and (0.53 ±0.11);p21 protein was (0.49 ±0.08),(0.97 ±0.09) and (1.55 ±0.13);Caspase-3 protein was (0.36 ± 0.05),(0.67 ± 0.10) and (0.89 ± 0.11);the relative expression of Bcl-2 protein in each group was (0.61 ± 0.10),(0.48 ± 0.05) and (0.24 ± 0.08).Gli1,Shh mRNA and Gli1,Shh protein expression were decreased.AnnexinV-FITC double staining showed Lanthanum Citrate group and KAAD-cyclopamine group had increased apoptosis rate of SMMC-7721 cells by flow cytometry.Conclusion Lanthanum Citrate inhibits the proliferation and promotes apoptosis in hepatocellular carcinoma SMMC-772 cells through suppressing hedgehog signaling pathway.