基于白细胞介素-11受体α靶点的131I-CGRRAGGSC对乳腺癌细胞的抑制作用  

Inhibitory effect of interleukin -11 receptor α- targeted 131I- CGRRAGGSC on human breast cancer cells

作　　者：胡瑶[1] 孙晋[1] 李天女[1] 刘璐[3] 刘圣[2] 施海彬[2] 周殡 陈道桢[5] 

机构地区：[1]南京医科大学第一附属医院PET/CT中心,210029 [2]南京医科大学第一附属医院放射科,210029 [3]东南大学附属中大医院核医学技术研究所,南京210009 [4]山东中医药大学第二附属医院神经外科,济南250001 [5]无锡市妇幼保健院中心实验室,214002

出　　处：《中华实验外科杂志》2018年第1期65-68,共4页Chinese Journal of Experimental Surgery

基　　金：江苏省“六大人才高峰”项目（2013-WSN-039）;江苏省卫生计划生育委员会基金项目（Z201502）;国家自然科学基金（81202032、81372480）;南京市科技局基金（201303038）;江苏省高校自然科学面上项目（16KJB320004）

摘　　要：目的通过氯胺-T法构建基于白细胞介素-11受体α（IL-11Rα）靶点的标记产物131I-CGRRAGGSC，观察其对高表达IL-11Rα乳腺癌细胞抑制作用。方法采用氯胺-T法碘标酪氨酸修饰CGRRAGGSC；噻唑蓝（MTT）法、Transwell和划痕实验检测131I-CGRRAGGSC对乳腺癌细胞增殖及迁移的影响；Western blot检测0.000、2.775、5.550 MBq/ml 131I-CGRRAGGSC处理乳腺癌细胞24 h后，细胞内IL-11Rα和信号转导与转录激活因子3（STAT3）、磷酸化STAT3（p-STAT3）蛋白的表达变化。结果成功制备131I-CGRRAGGSC，其放化纯度达95%以上；不同浓度131I-CGRRAGGSC（4.625、9.250、18.500、37.000 MBq/ml）对乳腺癌细胞MDA-MB-231和MCF-7的增殖抑制率分别是（21.46±1.08）%、（37.95±2.59）%、（49.18±0.77）%、（60.34±0.19）%（F＝389.4，P＝0.000）和（27.59±2.15）%、（41.67±0.92）%、（54.53±1.07）%、（64.84±1.69）%（F＝328.6，P＝0.000）；Transwell结果显示2.775、5.550 MBq/ml 131I-CGRRAGGSC对乳腺癌细胞MDA-MB-231和MCF-7的迁移抑制率分别是（32.05±4.44）%、（45.92±2.55）%（t＝4.688，P＝0.009）和（21.99±1.18）%、（39.45±1.36）%（t＝16.760, P＝0.000）；划痕实验也证实131I-CGRRAGGSC抑制MDA-MB-231细胞，而对MCF-7细胞作用不明显；Western blot检测发现随着131I-CGRRAGGSC浓度的增加，其处理乳腺癌细胞24 h后细胞内IL-11Rα、p-STAT3蛋白均逐渐降低，而STAT3蛋白的表达无明显变化。结论131I-CGRRAGGSC对乳腺癌细胞迁移有抑制作用，可能与IL-11Rα阻断STAT3的磷酸化相关。Objective To establish interleukin -11 receptor α （IL-11Rα）-based 131I-CGRRAGGSC by chloramines-T method, and explore the inhibitory effects of 131I-CGRRAGGSC on human breast cancer cells overexpressing IL-11Rα.MethodsThe tyrosine modified CGRRAGGSC protein was labeled with 131I by chloramines-T method. Methyl thiazol tetrazolium （MTT）, Transwell and wound-healing assay were used to detect the effects of 131I-CGRRAGGSC on the migration and proliferation of human breast cancer cells. Western blotting was used to detect the protein expression of IL-11Rα, phosphorylated signal transducer and activators of transcription 3 （p-STAT3） and signal transducer and activators of transcription 3 （STAT3） in breast cancer cells after treatment with 0, 2.775 and 5.550 MBq/ml 131I-CGRRAGGSC.Results131I-CGRRAGGSC was radiolabeled successfully and radiochemical purity after purification was over 95%. The inhibition ratio of breast cancer cells （MDA-MB-231 and MCF-7） was （21.46±1.08）%, （37.95±2.59）%, （49.18±0.77）%, （60.34±0.19）% （F=389.4, P=0.000） and （27.59±2.15）%, （41.67±0.92）%, （54.53±1.07）%, （64.84±1.69）% （F=328.6, P=0.000） after 131I-CGRRAGGSC treatment （4.625, 9.250, 18.500 and 37.000 MBq/ml, respectively）. Transwell demonstrated that the migration ratios of 2.775, 5.55 MBq/ml 131I-CGRRAGGSC were （32.05±4.44）%, （45.92±2.55）% （t=4.688, P=0.009） for MDA-MB-231 cells and （21.99±1.18）%, （39.45±1.36）% （t=16.760, P=0.000） for MCF-7 cells, respectively. Wound-healing assay also suggested that 131I-CGRRAGGSC inhibited MDA-MB-231 cells, but not MCF-7 cells. The cellular IL-11Rα and p-STAT3 levels were decreased in a dose-dependent manner whereas the STAT3 level had no significant change in 131I-CGRRAGGSC-treated breast cancer cells after 24 h in compared to those in the control cells.Conclusion131I-CGRRAGGSC could inhibit the migration and proliferation of human breast cancer cells by down-regulating the IL-11Rα to inhibit STAT3 ac

关 键 词：乳腺癌 放射性标记 迁移 131I 

分 类 号：R737.9[医药卫生—肿瘤]