Inhibitory effects of 125I radioactive particle implantation combined with CIK cells on the growth of human hepatocellular carcinoma xenografts in nude mice

Abstract:

Objective：To observe the inhibitory effects of 125I interstitial brachytherapy combined with cytokine-induced killer（CIK） cells on the growth of human hepatocellular carcinoma（HCC） xenografts in nude mice. Methods：Peripheral blood mononuclear cells were taken from health people and different cytokines were added to promote the mature of CIK cells. CIK cell phenotype was detected by flow cytometry；CD3+CD56+ double positive cells reaching 20% was considered as qualified. BALB/c nude mice were transplanted with SMMC-7721 HCC cell to establish tumor model and the mice were divided into 125I radioactive particle group（group A），CIK cell group（group B），125I radioactive particle + CIK cell group（group C） and blank control group（group D）. Treat－ment was given respectively，diameters of tumors in each group were measured every 4 d and inhibitory effects of different treatments on growth of HCC xenografts were observed. Pathological changes of xenografted tumors were detected by HE staining，histo-pathol－ogy and apoptotic rate of these tumors were examined by TUNEL；expressions of Ki-67 protein were detected by immunohistochemical staining. Results：125I radioactive particle implantation combined with CIK cells intravenously can significantly inhibit the growth of HCC xenografts in nude mice. In group C，tumor volume was （0.42±0.17） cm3，less than those in group A（1.23±0.83） cm3，group B（3.77±1.42） cm3 and group D（6.62 ± 0.53） cm3，with significant differences among groups（F=155.706，P<0.001）.Inhibition rate in group C was 93.71%，significantly higher than those in group A（81.33%） and group B（43.06%）. Immunohistochemical staining re－vealed that mean absorbance value of Ki-67 protein in each group were：group C（0.481±0.063），group A（0.592±0.104），group B（0.669±0.120），group D（0.797±0.113） respectively，with statistically significant differences among groups（F=24.334，P<0.001）. According to the results of TUNEL，apoptotic mean absorbance value in group C was （0.859±0.067），higher than that in group A （0.756±0.055） and group B（0.517±0.051） respectively，with statistically significant differences in each group（F=318.373，P<0.001）. Conclusions：Permanently implanted radioactive 125I particle combined with CIK cells immune therapy can significantly inhibit the growth of HCC xenografts in nude mice，restrain the proliferation of tumor and induce apoptosis in vivo，thus it could become a thera－py for hepatoma.