The killing effect of <sup>131</sup>Ⅰ-labeled B2-S22-AFA on breast cancer cells with high HER-2 expression

Yamei LI; Yanxing GUAN; Xuezhong CHEN; Qing ZHANG; Qing ZHANG; Mengzhi ZHANG

doi:10.11889/j.0253-3219.2017.hjs.40.120301

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The killing effect of ¹³¹Ⅰ-labeled B2-S22-AFA on breast cancer cells with high HER-2 expression

NUCLEAR CHEMISTRY, RADIOCHEMISTRY, RADIOPHARMACEUTICALS AND NUCLEAR MEDICINE | 更新时间：2021-05-19

- The killing effect of ¹³¹Ⅰ-labeled B2-S22-AFA on breast cancer cells with high HER-2 expression
  封面论文
- NUCLEAR TECHNIQUES Vol. 40, Issue 12, Article number: 120301(2017)
- 作者机构：
  
  南昌大学第一附属医院核医学科南昌 330006
- 作者简介：
- 基金信息：
  
  Ganpo Excellence 555 Project and Natural Science Fund Project of Jiangxi Province
- DOI：10.11889/j.0253-3219.2017.hjs.40.120301
  CLC： R817.8
- Received：21 March 2017，
  
  Revised：19 October 2017，
  
  Published：10 December 2017
- 稿件说明：
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Yamei LI, Yanxing GUAN, Xuezhong CHEN, et al. The killing effect of ¹³¹Ⅰ-labeled B2-S22-AFA on breast cancer cells with high HER-2 expression[J]. Nuclear techniques, 2017, 40(12): 120301
DOI：

Yamei LI, Yanxing GUAN, Xuezhong CHEN, et al. The killing effect of ¹³¹Ⅰ-labeled B2-S22-AFA on breast cancer cells with high HER-2 expression[J]. Nuclear techniques, 2017, 40(12): 120301 DOI： 10.11889/j.0253-3219.2017.hjs.40.120301.

摘要

人类表皮生长因子受体2（Human Epidermal Growth Factor Receptor 2，HER-2）是乳腺癌最重要的致病基因。本文探讨

131

Ⅰ标记的HER-2特异结合小分子模拟肽B2-S22-AFA对乳腺癌细胞的特异性杀伤作用。采用溴代琥珀酰亚胺法（N-Bromide Succinimide，NBS）进行

131

Ⅰ标记B2-S22-AFA，测定标记率、放化纯度、稳定性及免疫活性。用Western Blot法和免疫组化法测定人乳腺癌SKBR3及MDA-MB-231Her-2细胞HER-2表达，观察不同浓度表皮生长因子（Epidermal Growth Factor，EGF）条件下B2-S22-AFA对细胞生长的抑制率。设B2-S22-AFA组（B2-S22-AFA终浓度1 μg·mL

-1

）、

131

Ⅰ-B2-S22-AFA组（

131

Ⅰ-B2-S22-AFA终浓度144 kBq·μg

-1

·mL）、

131

Ⅰ组（

131

Ⅰ终浓度144 kBq·mL

-1

）、阴性对照组及试剂空白组，每组EGF终浓度均5.0 pg·mL

-1

，采用四唑盐比色法（Methyl Thiazolyl Tetrazolium，MTT）测定SKBR3和MDA-MB-231细胞增殖活性，观察

131

Ⅰ-B2-S22-AFA、B2-S22-AFA及

131

Ⅰ作用不同时间对两种细胞生长的抑制率。结果显示，HER-2在SKBR3细胞呈强阳性表达，在MDA-MB-231细胞呈弱（或低）表达。

131

Ⅰ-B2-S22-AFA标记率、放化纯度及比活度分别为64.8%-79.6%、95.0%-97.6%、151.7 MBq·mg

-1

，在37℃血清中放置4 h、12 h、24 h、48 h、72 h的放化纯度分别95.4%、93.5%、91.4%、88.2%、77.4%，

131

Ⅰ-B2-S22-AFA与SKBR3细胞及MDA-MB-231细胞的最大结合率分别（66.47±3.24）%和（3.89±0.81）%（3次）。当EGF存在时，B2-S22-AFA可明显抑制SKBR3细胞生长；无EGF时，B2-S22-AFA无此作用。

131

Ⅰ-B2-S22-AFA对SKBR3细胞的杀伤作用较B2-S22-AFA和

131

Ⅰ明显增强（均

0.05），B2-S22-AFA对SKBR3细胞杀伤作用显著高于

131

Ⅰ（

0.05），

131

Ⅰ-B2-S22-AFA和B2-S22-AFA对MDA-MB-231细胞均无杀伤作用。综上所述，

131

Ⅰ-B2-S22-AFA可显著加强、加速B2-S22-AFA对HER-2高表达乳腺癌细胞的特异性杀伤作用。

Abstract

Background

B2-S22-AFA is a kind of small molecule mimetic polypeptide that can conjugate to epidermal growth factor receptor 2 (HER-2) specifically and has obvious depressant effect on breast cancer cells with overexpressing HER-2.

Purpose

This study aims to investigate the specific killing effect of

131

Ⅰ-labeled B2-S22-AFA on breast cancer cell with overexpressing HER-2.

Methods

131

Ⅰ-B2-S22-AFA was prepared by using N-bromosuccinimide method to measure the labeling efficiency

radiochemical purity

stability

and immunocompetence. The expression levels of HER-2 in SKBR3 and MDA-MB-231 cells were detected by Immunohistochemistry and Western Blot. The inhibitory rate of B2-S22-AFA on cell growth was observed with epidermal growth factors (EGF) at different concentrations. Five groups i.e

B2-S22-AFA group (B2-S22-AFA final concentration:1 μg·mL

-1

)

131

Ⅰ-B2-S22-AFA group (

131

Ⅰ-B2-S22-AFA final concentration:144 kBq/1 μg·mL

-1

)

131

Ⅰ group (

131

Ⅰ final concentration:144 kBq·mL

-1

)

negative control group and reagent blank group

were selected for contrast tests with the final concentration of EGF in each group at 5.0 pg·mL

-1

. The proliferation and activity of cells were measured by Methyl thiazolyl tetrazolium assay. The inhibitory rates were compared among

131

Ⅰ-B2-S22-AFA group

B2-S22-AFA group and

131

Ⅰ group in the growth of the two kinds of cells at different time.

Results

1) HER-2 receptors were strongly expressed in SKBR3 cells while weakly (low) or no expressed in MDA-MB-231 cells. The radiochemical purity

labeling rate and specific activity of

131

Ⅰ-B2-S22-AFA were 95.0%-97.6%

64.8%-79.6% and 151.7 MBq·mg

-1

respectively. Radiochemical purity of

131

Ⅰ-B2-S22-AFA was 95.4%

93.5%

91.4%

88.2% and 77.4% when it was placed at 37℃ in serum for 4 h

12 h

24 h

48 h and 72 h

respectively. The maximum binding rates of SKBR3 and MDA-MB-231 cells were (66.47±3.24)% and (3.89±0.81)% (tested for 3 times) respectively. 2) The inhibitory effect of B2-S22-AFA on the growth of SKBR3 cells only in the presence of EGF. 3) The killing effect of

131

Ⅰ-B2-S22-AFA on SKBR3 cells was significantly stronger than that of B2-S22-AFA and

131

Ⅰ (

0.05)

and the inhibitory effect of B2-S22-AFA on the growth of SKBR3 cells was significantly higher than that of

131

Ⅰ (

0.05).

131

Ⅰ-B2-S22-AFA and B2-S22-AFA had no obvious killing effect on MDA-MB-231 cells.

Conclusion

131

Ⅰ-B2-S22-AFA can significantly enhance and accelerate the specific killing effect of B2-S22-AFA on breast cancer cells with high HER-2 expression.

关键词

Keywords

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The killing effect of 131Ⅰ-labeled B2-S22-AFA on breast cancer cells with high HER-2 expression

DOI：10.11889/j.0253-3219.2017.hjs.40.120301

摘要

Abstract

关键词

Keywords

references

The killing effect of ¹³¹Ⅰ-labeled B2-S22-AFA on breast cancer cells with high HER-2 expression