【摘要】 目的探讨含非甲基化CpG二核苷酸的寡脱氧核苷酸(cytosine-phosphate-guanine oligodeoxynucleotide,CpG ODN)对卡铂治疗Lewis肺癌荷瘤小鼠免疫功能的影响。方法在小鼠右前腋窝接种Lewis肺癌细胞,制备荷瘤小鼠模型,将32只荷瘤小鼠随机分为4组:荷瘤对照组,不做任何处理;卡铂治疗组,第1-5天每天腹腔注射卡铂注射液0.32 mg;CpG组,第1-5天每次腹腔注射CpG ODN1826 0.05 mg;CpG+卡铂组,每次卡铂注射前6小时腹腔注射CpG ODN1826;另设空白对照组。观察各组移植瘤生长速度和重量,小鼠血清中TNF-α和IL-12含量,脾指数和胸腺指数。结果成功建立荷瘤小鼠模型,各治疗组小鼠肿瘤体积都较对照组明显减小(P<0.01),CpG+卡铂组移植瘤体积最小;卡铂组、CpG组、CpG+卡铂组的抑瘤率分别为23.4%、21.5%、48.4%;空白组小鼠血清含量TNF-α、IL-12分别为(105.8±9.9)μg/L、(16.56±0.99)ng/L;对照组:(125.5±18.4)μg/L、(17.87±1.11)ng/L,CpG组:(199.0±8.4)μg/L、(24.56±1.2)ng/L;卡铂组:(70.4±8.7)μg/L、(12.50±1.15)ng/L;CpG+卡铂组:(127.8±17.3)μg/L、(16.32±0.73)ng/L;空白组小鼠脾指数、胸腺指数分别为(8.64±0.82)mg/g、(2.55±0.24)mg/g;对照组:(11.11±1.6)mg/g、(2.96±0.29)mg/g;CpG组:(16.01±1.83)mg/g、(3.31±0.27)mg/g;卡铂组:(8.27±1.12)mg/g、(1.81±0.8)mg/g;CpG+卡铂组:(12.58±1.58)mg/g、(2.46±0.25)mg/g。CpG组的各种免疫指标都显著高于对照组(P<0.05),也显著高于卡铂组(P<0.001);而卡铂组的各种免疫指标都显著低于对照组(P<0.01)。并且,联合治疗组的各种指标都显著高于卡铂组(P<0.001)。结论 CpG ODN1826能通过激活机体免疫系统,提高机体的免疫功能,明显提高Lewis肺癌移植瘤对卡铂治疗的化疗敏感性。更多还原

【Abstract】 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(P<0.01),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(P<0.05),and were higher than those in carboplatin group also;But,All immune indexes in carboplatin group were lower than those in control group(P<0.01).Moreover,all immune indexes in combination group were higher than those in carboplatin group(P<0.001).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.更多还原