Effects of sorafenib combined with dendritic cells and cytokine induced killer cells on the growth and invasion and metastasis of hepatocellular carcinoma

Abstract

Objective To investigate the effects of sorafenib combined with dendritic cells and cytokine induced killer (DC-CIK) cells on the growth,invasion and metastasis of hepatocellular carcinoma.Methods CIK cells and dendritic cells from healthy adults were cultured in vitro.Mice models with H22 hepatic cancer were established,and randomly divided into the normal saline group,sorafenib group,DC-CIK group and the sorafenib + DC-CIK group according to the random number table.There were 40 rats in each group.All the mice received intragastric gavage with sorafenib of 100 μg/g once a day.DC-CIK cells were intraperitoneally injected into the mice every 3 days with 1 × 107 cells each time.Twenty mice bearing tumors in each group were sacrificed after treatment for 3 weeks,and the peripheral venous blood and hepatic tumor tissues were harvested.The levels of alphafetoprotein (AFP) were detected by ELISA,and the necrotic degree of tumor tissues was evaluated by hematoxylin and eosin staining.The protein expressions of Ki-67 and CD34 in the tumor tissues were determined by immunohistochemical method.The survival time of the other 20 mice bearing the tumor in each group were detected.All data were analyzed using the analysis of variance or LSD test.Results CIK cells and dendritic cells were successfully cultured.The levels of AFP in the peripheral venous blood of the normal saline group,sorafenib group,DC-CIK group and sorafenib + DC-CIK group were (0.675 ± 0.177) rg/L,(0.379 ± 0.052) ng/L,(0.415 ± 0.028) ng/L,(0.288 ± 0.012) ng/L,with significant difference between the 4 groups (F =0.415,P ＜ 0.05).The numbers of intrahepatic and peritoneal metastasis of the normal saline group,sorafenib group,DC-CIK group and sorafenib + DC-CIK group were 21.2 ± 1.3 and 29.7 ± 7.6,16.4 ± 1.6 and 17.4 ± 1.8,20.2 ± 1.7 and 26.4 ± 1.7,15.2 ± 1.3 and 15.2 ± 1.3,with significant difference between the 4 groups (F =2.137,3.271,P ＜0.05).The tumor inhibition rate of the normal saline group,sorafenib group,DC-CIK group and sorafenib + DC-CIK group were 0,21％ ± 3％,9％ ± 3％ and 24％ ± 5％,with significant difference between the 4 groups (F =3.715,P ＜0.05).The survival time of mice in the normal saline group,sorafenib group,DC-CIK group and sorafenib ± DC-CIK group were (18.2 ± 2.5) days,(21.6 ± 2.1) days,(24.3 ± 2.8) days and (25.4 ± 1.4) days,with significant difference between the 4 groups (F =6.247,P ＜ 0.05).Conclusions Sorafenib combined with immunotherapy can significantly increase the therapeutic effects of molecular targeted drug on hepatocellular carcinoma. Key words: Liver neoplams; Sorafenib; Dendritic cells; Cytokine induced killer cells; Mice