^(131)I-Herceptin对高表达HER-2/neu肺癌细胞增殖的影响

Inhibitory effects of ^(131)I-Herceptin on overexpressedH ER-2/neu overexpressed in lung cancer cell

目的探讨^(131)I-Herceptin对高表达HER-2/neu肺癌细胞增殖的影响。方法应用Iodogen法制备^(131)I-Herceptin,用TLC测定标记率及放化纯。实验设^(131)I-Herceptin组、Herceptin组、^(131)I组和生理盐水对照组。根据药物浓度及^(131)I的放射性活度分为三组:低剂量组:5 k Bq^(131)I-Herceptin、5μg/μl Herceptin、5 k Bq^(131)I和生理盐水;中剂量组:10 k Bq^(131)I-Herceptin、10μg/μl Herceptin、10 k Bq^(131)I和生理盐水;高剂量组:20 k Bq^(131)I-Herceptin、20μg/μl Herceptin、20 k Bq^(131)I和生理盐水。MTT法检测各组对人肺腺癌Calu-3细胞的生长抑制作用。结果^(131)I-Herceptin的标记率为(78.3±3.2)%,分离纯化后放化纯为(93.8±3.4)%。^(131)I-Herceptin对人肺腺癌Calu-3细胞的免疫结合率为(61.8±2.8)%。5、10、20 k Bq^(131)I-Herceptin人肺腺癌Calu-3细胞抑制率,分别为(36.7±2.5)%、(40.3±3.2)%、(43.6±3.5)%;质量浓度为5μg/μl、10μg/μl、20μg/μl的未标记Herceptin抑制率,分别为(28.3±3.0)%、(30.5±2.6)%、(32.4±2.4)%;5、10、20 k Bq^(131)I抑制率,分别为(8.3±1.8)%、(9.8±1.0)%、(11.2±2.3)%;生理盐水对照组自然凋亡率为(3.5±0.6)%。^(131)I-Herceptin、Herceptin、^(131)I不同浓度间的细胞抑制率差异有统计学意义(P<0.05)。^(131)I-Herceptin高剂量组的细胞抑制率高于低剂量组、中剂量组(P<0.05)。高剂量组:^(131)I-Herceptin组的细胞抑制率最高,与Herceptin组的差异有统计学意义(P<0.05);与^(131)I组、对照组的差异有统计学意义(P<0.05)。结论^(131)I-Herceptin能与人肺腺癌Calu-3细胞特异性结合,并对人肺腺癌Calu-3细胞增殖有显著的抑制作用。

Objective To explore the inhibitory effects of ^131I -Herceptin on overexpressed HER -2/neu overexpressed in lung cancer cell. Methods Herceptin was labeled with ^131I using the Iodogen method. The radiolabeling efficiency and radiochemical pu- rity were characterized by TLC in vitro. There were four groups including ^131I - Herceptin, Herceptin, ^131I and 0.9% sodium chloride solution group. It was divided into three groups according to the drug concentration and ^131I radioactive activity. 5kBq ^131I - Herceptin,5μg/ μl Herceptin ,5kBq ^131I and physiological saline was classified as low dose group. 10kBq 131I -Hereeptin, 10μg/ μl Herceptin, 10kBq ^131I and physiological saline was classified as medium dose group. 20kBq ^131I - Herceptin,20μg/ μl Herceptin, 20kBq ^131I and physiological saline was classified as high dose group. The inhibitory effects of different treatments on the proliferation of human lm.g adenocarcinoma cell line Calu - 3 were measured by MTr assay. Results The labeled rate of ^131I - Hereeptin was （78.3 ± 3.2） %. The radiochemical purity of ^131I- Herceptin was （93.8 ± 3.4 ） % after purification. The immune combination rate of^131I - Herceptin was （61.8 ± 2.8 ） % for lung adenocareinoma cell line Calu -3. Cell inhibition rates of 5,10,20kBq ^131I -Herceptin to human lung adenocarcinoma Calu -3 were （ 36.7 ±2.5 ） %, （40.3 ± 3.2） %, （ 43.6 ± 3.5 ） % respectively. Cell inhibition rates of 5,10,20μg/μl Herc eptin were （ 28.3± 3.0）%, （30.5±2.6）% ,（32.4 ±2.4）% respectively. Cell inhibition rates of 5,10,20kBq ^131I were （8.3 ± 1.8）%, （9.8 ± 1.0）%, （ 11.2 ± 2.3 ） % respectively. Natural apoptosis rate of physiological saline was （ 3.5± 0.6） %. The cell inhibition rate between different concentrations of ^131I- Hereeptin, Herceptin, ^131I haved significant difference （ P 〈 0.05 ）. Cell inhibition rate of high dose group of ^131I - Herceptin was higher than low and medium dose group（ P 〈 0. 05 ）. Cell inhibition rate of ^131I - Herceptin group was the highest in high dose group. It was statistically significant between ^131I - Herceptin and Herceptin （ P 〈 0.05 ）. It was obviously statistically significant among ^131I- Hereeptin, ^131I and physiological saline （ P 〈 0. 05）. Conduslon ^131I - Herceptin can bind to human lung adenocarci- noma Calu -3 with highly affinity and has significant inhibitory effect on the lung cancer cell line.