低剂量^(131)I标记的抗癌胚抗原抗体C50联合化疗诱导裸鼠结直肠癌移植瘤细胞凋亡

Induction of tumor cell apoptosis in colorectal cancer xenografts of nude mice with low dosage of ^(131) I-labelled anti-carcinoembryonic antigen antibody C50 combined with chemotherapy

目的 从诱导细胞凋亡的角度 ,探讨低剂量13 1I标记的抗癌胚抗原 (CEA)单抗C5 0 (13 1I C5 0 )对结直肠癌移植瘤的治疗作用及联合 5 氟尿嘧啶 (5 FU)化疗的效果。方法 建立表达CEA的人LoVo结直肠癌荷瘤裸鼠模型。接种第 9天 ,分别采用 5 FU、75 μCi13 1I C5 0及 5 FU联合13 1I C5 0尾静脉注射治疗裸鼠移植瘤。接种第 15天 ,肿瘤组织进行HE染色和末端脱氧核糖核酸转移酶介导的荧光素 dUTP缺口末端标记法 (TUNEL法 )凋亡细胞染色 ,计算肿瘤细胞凋亡指数。结果 光学显微镜下各组裸鼠移植瘤组织未见细胞溶解、坏死表现。TUNEL法染色示空白对照组、化疗组、放射免疫治疗(RAIT)组及RAIT +化疗组的凋亡指数分别为 (0 .2 9± 0 .0 8) % ,(18.6 8± 2 .6 9) % ,(4 0 .88± 4.5 4) %和(6 2 .33± 8.0 0 ) % ,各组两两之间凋亡指数差异均有显著性 (P值均 <0 .0 0 1)。结论 低剂量RAIT可通过诱导肿瘤细胞凋亡达到治疗结直肠癌的目的 ,RAIT联合 5

Objective To investigate the outcome of induction of tumor cell apoptosis with low dosage of 131 I labelled anti carcinoembryonic antigen(CEA) monoclonal antibody C50( 131 I C50) and the therapeutic efficacy of combining radioimmunotherapy(RAIT) with chemotherapy in colorectal cancer xenografts. Methods Human colorectal cancer xenografts with positive CEA expression were established in nude mice with LoVo cell line. 5 fluorouracil(5 FU), 75 μCi 131 I C50, and 5 FU, combined with 131 I C50 were given to nude mice through tail vein to treat xenografts on 9th day after implantation of tumor cells. Fifteen days after implantation, each mouse was sacrificed and tumor tissues were stained with HE and terminal deoxynucleotidyl transferase mediated X DUTP nick end labeling technique(TUNEL technique). Apoptosis index(AI) of xenograft cells in each mouse was calculated. Results Under light microscope, no obvious cytolysis or necrosis of tumor cells was seen in all four groups. Apoptosis indexes in blank control group, chemotherapy group, radioimmunothera py(RAIT) group, and RAIT+chemotherapy group were (0.29±0.08)%, (18.68± 2.69 )%,(40.88 ±4.54 )% and (62.33±8.00)%, respectively. There were significant difference of apoptosis indexes between any groups( P <0.001). Conclusions Low dosage of RAIT can play an anti tumor role in colorectal cancer by leading apoptosis of tumor cells. The outcome of induction of tumor cell apoptosis can be enhanced by combining RAIT with chemotherapy.