In vitro and in vivo cytotoxicity effects of co-cultured DC CIK cells combined with sorafenib against hepatocellular carcinoma
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Abstract:
Objective:To investigate the in vitro and in vivo inhibitory effects of DC (dendritic cell)CIK (cytokineinduced killer cell) cocultured cells combined with sorafenib against hepatocellular carcinoma cell line BEL7402. Methods: DC and CIK cells were generated in vitro by stimulating human peripheral blood mononuclear cells with different cytokines, and then they were cocultured. The cytotoxicity of DCCIK cocultured cells (DCCIK) combined with sorafenib against BEL7402 cells was determined by CCK8 kit. The apoptosis of BEL7402 cells was measured by Annexin VFITC Kit. BEL7402implanted tumor model was established by subcutaneous injection in nude mouse. Tumorbearing mice were divided into normal saline control group, sorafenib group, DCCIK group and DCCIK+sorafenib group. The inhibitory effects were observed in different groups. Results: The cytotoxicity rate of BEL7402 cells in DCCIK+sorafenib group was significantly higher than those in the other two groups, with cytotoxicity rate in DCCIK+sorafenib group being (75.24±1.91)%, which was 1.8 times that in DCCIK group and 2.1 times that in sorafenib group (P<0.01). The apoptosis rate of BEL7402 cells in DCCIK+sorafenib group was significantly higher than those in the sorafenib and DCCIK groups, with the apoptosis rate in DCCIK+sorafenib group being (78.32±2.54)% (P<0.05). The volume of tumor in the combination group was significantly smaller than those in the other groups (P<0.05). In vivo results showed that DCCIK+sorafenib treatment significantly inhibited the growth of BEL7402implanted tumors, and the inhibitory rate was (83.37 ±0.16)%, which was significantly higher than those of the other groups (P<0.01). Conclusion:DCCIK cocultured cells combined with sorafenib can inhibit the growth of hepatocellular carcinoma cell line BEL7402 in vitro and in vivo. Molecular targeting therapy combined with immunotherapy may be a new way for the comprehensive treatment of hepatocellular carcinoma.
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Project supported by the Key Science and Technology Development Program of Liaoning Province (No.20082250085)