射频消融联合胞嘧啶鸟嘌呤寡脱氧核苷酸治疗小鼠乳腺癌皮下模型

摘要

目的 观察射频消融联合瘤周注射胞嘧啶鸟嘌呤寡脱氧核苷酸(CpG ODN)对BALB/c小鼠皮下种植性乳腺癌的治疗作用及对荷瘤鼠免疫功能的影响.方法 32只BALB/c小鼠双侧胁肋部皮下接种乳腺癌细胞EMT-6,建立乳腺癌动物模型,随机分为4组,每组8只,分别给予左侧皮下肿瘤射频消融+瘤周注射CpG ODN、射频消融、瘤周注射CpG ODN和瘤周注射生理盐水4种处理.定期测量治疗侧及非治疗侧肿瘤大小,尾静脉取血法收集各组小鼠外周血,酶联免疫吸附试验(ELISA)法检测血清白细胞介素(IL)-12、IL-10、IL-2及干扰素(IFN)-γ含量.当非治疗侧肿瘤直径达到18mm时手术切除肿瘤,并记录为非治疗侧观察终点,当治疗侧肿瘤直径达到18 mm时或出现恶病质时处死小鼠,记录生存时间.结果 射频消融+瘤周注射CpG ODN组和射频消融组治疗侧肿瘤体积体积显著小于CpG ODN组和对照组(P＜0.05).射频消融+瘤周注射CpG ODN组未治疗侧的肿瘤体积在第21天后明显小于其他各组(P＜0.05).射频消融+瘤周注射CpG ODN组中位生存时间为92 d,射频消融组为84d,瘤周注射CpG ODN组为64d,对照组为60d.射频消融+瘤周注射CpG ODN组小鼠外周血中IL-12浓度为312.40 ng/L,IL-10浓度为216.34 ng/L,IL-2浓度为75.33 ng/L,IFN-γ浓度为69.32 ng/L,显著高于其他3组(P＜0.05).结论 射频消融联合瘤周注射CpG ODN能激活小鼠体内的抗肿瘤免疫效应,起到抑制肿瘤生长作用.%Objective To investigate the efficacy of microwave ablation combined with peritumoral injected cytosine phosphate guanine oligodeoxyribonucleotide (CpG ODN) in inducing immunityresponse against mouse breast cancer.Methods Bilateral breast cancer model was established by subcutaneous injection EMT-6 cells underneath both sides of the BALB/c mouse rib area.According the therapy method to the left side tumor,there were 32 mice were divided randomly into four groups:combination therapy group (microwave ablation combined with peritumoral injected CpG ODN),ablation therapy group,CpG ODN therapy group,and control group.Bilateral tumor volume and survive time were observed.Concentration of interleukin (IL)-12,IL-10,IL-2 and interferon (IFN)-γ in serum were detected by enzyme linked immunosorbent assay (ELISA) method.When the non-treatment side tumor reaches 18 mm in diameter,the tumor resection is carried on,and recorded as endpoint of this side.When the treatment side tumor reaches 18 mm in diameter or cachexia takes place,the mice will be killed and the survival time will be recorded.Results In the bilateral tumor model,the left tumor volumes in combination therapygroup and ablation therapy group were smaller than those in CpG ODN therapy group and control group,right tumor volumes in combination therapygroup were smaller than those in other group after 21 days.The median survive time in combination therapy group,ablation therapy group,CpG ODN therapy group,and control group were 92,84,64,60 days respectively.The serum concentrations of IL-2,IL-10,IL-12,IFN-γin combination therapy group were higher than those in other groups.Conclusion Microwave ablation combined with peritumoralinjection of CpG ODN can enhance the host antitumor immunityeffect and inhibit tumor growth.