PYM-BAG5和131I-BAC5联合导向治疗鼻咽癌的实验研究

背景与目的:现代的肿瘤治疗提倡综合治疗,肿瘤的导向综合治疗具有研究价值.本实验在研究鼻咽癌放射免疫治疗的基础上,观察平阳霉素(pingyangmycin,PYM)和131 I与鼻咽癌单抗BAC5的偶联物PYM-BAC5和131 I-BAC5对鼻咽癌细胞CNE2的联合抑制效果.方法:用葡聚糖T-40作中间载体偶联PYM和BAC5,用测定抑菌活性和免疫活性的方法鉴定偶联物.用氯胺T法制备131 I-BAC5.设置单独用药组(游离PYM,131 I-mIgG)、单独导向用药组(PYM-BAC5,131 I-BAC5)以及联合导向用药组(PYM-BAC5+131 I-BAC5)共5个实验组,用MTT法测定各药物组的抑制作用.结果:PYM-BAC5和游离PYM对CNE2的半数抑制浓度(IC50)分别为46.57 μg/ml和316.70 μg/ml;131 I-BAC5和131 I-mIgG对CNE2的IC50分别为4.42×105 Bq/ml和＞11.10×105 Bq/ml;联合用药组中PYM-BAC5的IC50为7.01 μg/ml,131 I-BAC5的IC50为0.54×105Bq/ml.结论:(1)导向用药组的抑瘤效果明显高于非导向组;(2)联合导向用药组的抑菌效果明显高于单独导向用药组.

Experimental study of combined target treatments using PYM-BAC5 and 131I-BAC5 to nasopharyngeal carcinoma

BACKGROUND & OBJECTIVE: Combined therapy has been advocated for modern tumor treatment; the combined target therapy is a valuable research direction. Based on the previous research of nasopharyngeal carcinoma (NPC) radioimmunotherapy, this experiment was designed to develop two immunoconjugates of the monoclonal antibody BAC(5):PYM-BAC(5) and (131)I-BAC(5), and to assess the inhibition effects of their combined treatment on the NPC CNE-2 cells cultured in vitro. METHODS: Dextran T40 was used as media to link PYM and BAC(5). The conjugate PYM-BAC(5) was identified by testing its immunoactivity and the inhibition to mycobacterium. BAC(5) was labeled with (131)I by Chloramin-T method. Five experimental groups were set up:(1)PYM-BAC(5) group, (2)free PYM group, (3)(131)I-BAC(5) group, (4)(131)I-mIgG group, (5)the combined target treatment group ( (131)I-BAC(5)+PYM-BAC(5)). The antitumor effects of the five groups were assessed with MTT method. RESULTS: The 50% inhibition doses(IC(50)) of PYM-BAC(5) group and PYM group were 46.57 microg/ml and 316.7 microg/ml, respectively. The IC(50) of (131)I-BAC(5) group and (131)I-mIgG group to CNE2 were 4.42 x 10(5) Bq/ml and >11.1 x 10(5) Bq/ml,respectively. In the combined target treatment group(PYM-BAC(5)+(131)I-BAC(5)),the IC(50) of PYM-BAC(5) was 7.01 microg/ml and of (131)I-BAC(5) was 0.54 x 10(5) Bq/ml, which much less than other separate treatment groups. CONCLUSION: The inhibition effects of the target treatment ((131)I-BAC(5) and PYM-BAC(5)) on the NPC CNE-2 cells are stronger than non-target treatment (free PYM and (131)I-BAC(5)). The combined target treatment of the two immune ((131)I-BAC(5)+PYM-BAC(5)) conjugates gets stronger inhibition effects than their separate treatment.