重组人胰腺RNase1有效靶向并清除前列腺癌细胞。

Q2 Biochemistry, Genetics and Molecular Biology Iranian Biomedical Journal Pub Date : 2024-12-01
Omid Mikaili, Zahra Kiadehi, Vida Khalatbari Limaki, Reza Goudarzi, Amin Ramezani, Nasrollah Erfani, Amir Maleksabet
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引用次数: 0

摘要

导读:靶向药物递送为直接向肿瘤部位特异性递送抗癌药物打开了一扇新的窗口。促性腺激素释放激素(GnRH)是一种十肽,由于其靶向特性,其在靶向药物递送中的潜在应用受到了关注。它表现出对其受体的高亲和力,在人类中不具有免疫原性。人类胰腺核糖核酸酶1 (hpRNase1)与生长激素、抗体及其衍生物等靶向部分融合后显示出抗癌特性。本研究旨在将GnRH靶向肽连接到hpRNase1的n端,以增强其对表达GnRH受体的细胞(GnRH- r)的特异性。方法与材料:设计、合成编码基因,在pET28a表达载体上克隆产生重组酶,在大肠杆菌BL21 (DE3)菌中表达。诱导表达后,通过SDS-PAGE和Western blot验证所得蛋白的身份。接下来,通过亲和层析纯化重组蛋白,并评估其对表达GnRH-R的癌细胞的细胞毒作用。结果:GnRH-hpRNase1嵌合蛋白显著抑制了PC-3 (p = 0.021)、LNCaP (p = 0.034)和AD-Gn (p = 0.041)细胞的增殖,而对阴性细胞AD-293的生长无显著影响(p = 0.081)。GnRH-hpRNase1对PC-3细胞的IC50值比未融合的hpRNase1降低约26.5倍(p = 0.036),并通过诱导细胞凋亡发挥其抑制生长的作用。结论和讨论:核糖核酸酶,特别是人类胰腺RNase1,已经显示出开发新疗法的有趣特征。然而,它们有两个主要缺点:(1)对RI敏感;(2)对癌细胞的特异性较差。我们发现,工程化的GnRH- hprnase1可以特异性靶向表达GnRH受体的细胞,并通过诱导细胞凋亡来抑制其增殖。由于该融合酶具有良好的抗肿瘤活性,因此可以进一步对表达gnrh - r的肿瘤异种移植物进行体内检测,以评估其抗肿瘤作用。
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25th National and 11th International Annual Congress on Research and Technology of Iranian Medical Sciences Students, Urmia, Iran, 5-7 September, 2024
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来源期刊
Iranian Biomedical Journal
Iranian Biomedical Journal Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
3.20
自引率
0.00%
发文量
42
审稿时长
8 weeks
期刊最新文献
25th National and 11th International Annual Congress on Research and Technology of Iranian Medical Sciences Students, Urmia, Iran, 5-7 September, 2024 25th National and 11th International Annual Congress on Research and Technology of Iranian Medical Sciences Students, Urmia, Iran, 5-7 September, 2024 25th National and 11th International Annual Congress on Research and Technology of Iranian Medical Sciences Students, Urmia, Iran, 5-7 September, 2024 25th National and 11th International Annual Congress on Research and Technology of Iranian Medical Sciences Students, Urmia, Iran, 5-7 September, 2024 25th National and 11th International Annual Congress on Research and Technology of Iranian Medical Sciences Students, Urmia, Iran, 5-7 September, 2024
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