Immunostimulatory effects of CpG ODN1826 upon murine Lewis lung cancer treated with carboplatin

Objective To investigate the effect of synthetic DNA sequences containing unmethylated cytosine-guanine motifs on Lewis lung cancer treated with carbplatin in mice.Methods The tumor-bearing mouse model was induced by injecting Lewis lung cancer cells into the right infra-axillary of 32 C57BL mice;the animals were evenly randomized into 4 groups: control group without treatment,carboplatin group treated with carboplatin only(0.32 mg/day,on day 1,2,3,4,5),CpG group receiving CpG ODN1826 0.05 mg on day 1,2,3,4,5;CpG + carboplatin group treated with CpG ODN1826 6 hours before carboplatin.The non tumor-bearing C57BL mice were used as blank controls.Tumor growth and tumor weight were observed in all groups.Serum TNF-α and IL-12 levels,the spleen index and thymus index were measured.Results The Lewis lung cancer-bearing model was successfully established in mice.The tumor volumes of treated groups were smaller than those in control group(P0.01),and the tumor volumes of CpG + carboplatin group was the smallest.The tumor inhibitory rates were 23.4% in carboplatin group,21.5% in CpG group C and 48.4% in CpG+carboplatin group.The serum concentrations of TNF-α and IL-12 were(105.8±9.9)μg/L and(16.56±0.99)ng/L in blank group,(125.5±18.4)μg/L and(17.87±1.11)ng/L in control group,(199.0±8.4)μg/L and(24.56±1.2)ng/L in CpG group,(70.4±8.7)μg/L and(12.50±1.15)ng/L in carboplatin group,(127.8±17.3)μg/L and(16.32±0.73)ng/L in CpG plus carboplatin group.The spleen and thymus index was(8.64±0.82)mg/g and(2.55±0.24)mg/g respectively in blank group;(11.11±1.6)mg/g and(2.96±0.29)mg/g in control group,(16.01±1.83)mg/g and(3.31±0.27)mg/g in CpG group,(8.27±1.12)mg/g and(1.81±0.8)mg/g in carboplatin group,(12.58±1.58)mg/g and(2.46±0.25)mg/g in CpG with carboplatin group.All immune indexes in CpG group were higher than those in control group(P0.05),and were higher than those in carboplatin group also;But,All immune indexes in carboplatin group were lower than those in control group(P0.01).Moreover,all immune indexes in combination group were higher than those in carboplatin group(P0.001).Conclusions CpG ODN1826 can dramatically increase the chemo-sensitivity of tumor cells by activating the immune system and elevate the immune function of tumor-bearing mice.