中文摘要：

目的研究^125I-伐普肽（RC-160）对转染人生长抑素2型受体（hSSTR2）基因的肺腺癌A549细胞（A549-hSSTR2）受体内化的规律，以及^125I-RC-160对A549-hSSTR2细胞的杀伤作用。方法采用放射性配基结合分析法，以^125I-RC·160为放射性配基，测定A549-hSSTR2细胞及未转染hSSTR2基因的A549（A549-pc3）细胞与^125I-RC-160在37℃温育不同时间（0．25，0．5，1，4，8，20和24h）的内化率；采用四甲基偶氮唑蓝（MTT）法测不同浓度^125I-RC-160、Na ^131I、RC-160对A549-hSSTR2细胞及A549-pc3细胞作用24，48，72和96h的杀伤作用。结果37℃条件下温育，^125I—RC-160迅速与A549-hSSTR2受体结合并使受体发生内化。在温育1h时，A549-hSSTR2细胞结合（膜结合＋内化）的放射性计数为总计数的（18．2±1．9）％，明显高于A549-pc3组[（5．7±1．4）％，P〈0．01]。1h后，A549-hSSTR2细胞膜受体内化率（内化部分放射性计数与总放射性计数比）随时间的延长继续增加，膜结合率（膜结合部分放射性与总放射性计数比）随时间的延长逐渐减少。至24h时，受体内化率达（13．0±1．1）％，膜结合率为（3．9±2．2）％。^125I-RC-160对A549-hSSTR2细胞的杀伤作用较对A549-pc3细胞明显增强，并呈一定的剂量-效应和时间-效应关系，在96h时，3700kBq／ml ^131I-RC-160对A549-hSSTR2的抑制率达（78．8±5．9）％。结论^125I-RC-160可以使转染hSSTR2基因的细胞膜受体内化；^131 I-RC-160对A549-hSSTR2细胞的杀伤作用较强，这为外源性受体基因介导核素靶向性内照射治疗肿瘤提供了实验依据。

英文摘要：

Objective Introducing new gene to make an useful expression of the host cell is of clinical potential. In the current study, the internalization of the radioiodinated somatostatin analog ^125I-RC- 160 by A549 lung carcinoma cells transfected with human somatostatin receptor subtype 2 （hSSTIL2） gene （A549-hSSTR2）, and the lethal effect of ^131I-RC-160 on A549-hSSTR2 cells were investigated. Methods A549-hSSTR2 cells expressing hSSTR2 or A549-pc3 cells without hSSTR2 expression were incubated at 37℃ with ^125I-RC-160 for different time（0.25,0.5, 1,4, 8, 20 and 24 h）. The internalization of the radioligand was determined at the end of incubation. By using 3-（4,5-dimethyhhiazol-2-yl）-2,5-diphenyhetrazolium bromide （MTT） assay, the lethal effect of various dosage of ^131I-RC-160, Na^131I, RC-160 on A549-hSSTR2 and A549-pc3 after 24, 48, 72, 96 h incubation were measured. Results ^125I-RC-160 was rapidly internalized mediated via the membrane receptor of A549-hSSTR2. The binding radioactivity of A549-hSSTR2 cells[ （18.2 ±1.9）% of total amount added] was higher than that of A549-pe3 cells （5.7± 1.4）% after 1 h of incubation （P 〈0.05 ）. The internalization showed time-dependent manner with concomitant decrease of membrane binding. ^131I-RC-160 had stronger growth-inhibit effect on A549-hSSTR2 cells than on A549-pc3 cells. Conclusion ^125I-RC-160 could internalize the A459-hSSTR2 cells with enhanced lethal effect than A549-pc3 control, proving the concept of exogenous receptor gene mediated internal radiation therapy of cancers.