低剂量131I标记的抗癌胚抗原抗体C50联合5-FU对结直肠癌裸鼠移植瘤生长的影响

背景与目的:癌胚抗原 (CEA)在结直肠癌组织中表达率高达 90%以上,本研究拟探讨低剂量 131I标记的抗 CEA单抗 C50( 131I- C50)及低剂量 131I- C50联合 5-氟尿嘧啶( 5- FU)对人结直肠癌移植瘤生长的影响.方法:建立表达 CEA的人 LoVo结直肠癌裸鼠移植瘤模型.接种第 9天,分别采用 5- FU、2775kBq 131I- C50及 5- FU联合 131I- C50尾静脉注射治疗荷瘤裸鼠.尾静脉给药后第 7天,每组各随机处死 2只荷瘤裸鼠,观察肿瘤细胞超微结构改变及组织病理学改变.计算各组裸鼠肿瘤体积、群体倍增时间及抑瘤率,比较接种第 30天的肿瘤体积.结果:对照组、5- FU组、131I- C50治疗组和 131I- C50联合 5- FU组接种第 30天肿瘤体积分别为 (9 765.19± 792.21)mm3、(6 533.75± 601.14)mm3、(5 413.57± 415.46)mm3和 (3 865.23± 263.57)mm3,四组之间差异均有显著性( P< 0.001);四组肿瘤群体倍增时间依次延长,分别为 3.07、3.09、3.18和 3.14天;后三组抑瘤率依次增大,分别为 30.97%、42.33%和 59.04%.结论:低剂量 131I- C50可抑制结直肠癌裸鼠移植瘤的生长,低剂量 131I- C50联合 5- FU可以增强抑制肿瘤生长的效果.

Influence of combination of low dosage 131I-labeled anti-carcinoembryonic antigen antibody C50 and 5-fluorouracil on tumor growth of colorectal cancer xenografts in nude mice

BACKGROUND & OBJECTIVE: The aim of this study was to investigate the influence of low dosage (131)I-labeled anti-carcinoembryonic antigen (CEA) monoclonal antibody C50 ((131)I-C50) on tumor growth and the therapeutic efficacy of combination of low dosage (131)I-C50 with chemotherapy using 5-fluorouracil (5-FU) on human colorectal cancer xenografts in nude mice. METHODS: Human colorectal cancer xenografts with positive CEA expression were established in nude mice with LoVo cell line. 5-FU, 2,775 kBq (131)I-C50, and 5-FU combined with (131)I-C50 were given to nude mice through tail vein to treat xenografts at 9(th) day after implantation of tumor cells. Two of the mice of each group were sacrificed randomly at 7(th) day after the treatment; and cellular ultrastructure of tumor tissues was examined under electron microscope. Pathological changes of tumor tissues were examined under light microscope. Tumor volume, tumor doubling time, and inhibition rate of each group were calculated. Tumor volumes of all groups at 30(th) day after implantation were compared with each other. RESULTS: There was significant difference of tumor volumes at 30(th) day after implantation between each other among control group, chemotherapy group, radioimmunotherapy (RAIT) group, and RAIT+chemotherapy group (P< 0.001). Tumor doubling time of these groups was prolonged and tumor inhibition rates increased successively. CONCLUSION: Low dosage (131)I-C50 can inhibit tumor growth of human colorectal cancer xenografts in nude mice. Efficacy of tumor growth inhibition can be enhanced by combination of low dosage (131)I-C50 with chemotherapy.