Potentiation of 177Lu-octreotate peptide receptor radionuclide therapy of human neuroendocrine tumor cells by PARP inhibitor.
Potentiation of 177Lu-octreotate peptide receptor radionuclide therapy of human neuroendocrine tumor cells by PARP inhibitor.
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DOI：
10.18632/oncotarget.25266
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发表时间：
2018-05-15
期刊：
影响因子：
--
通讯作者：
Beauregard, Jean-Mathieu
中科院分区：
文献类型：
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作者：
Purohit, Nupur K;Shah, Rashmi G;Beauregard, Jean-Mathieu
对于表达生长抑素受体的不可手术的神经内分泌肿瘤（NET）患者，使用177 Lu-[DOTA 0-Tyr 3]-奥曲酸（177 Lu-octreotate）的肽受体放射性核素治疗（PRRT）是最有前途的靶向治疗选择之一，但很少达到治愈。因此，正在测试不同的方法来提高NET患者中177 Lu-奥曲肽PRRT的疗效。使用胃肠胰腺BON-1和支气管肺癌NCI-H727作为NET细胞模型，在这里，我们报告了DNA修复相关酶聚（ADP-核糖）聚合酶-1（PARPi）的药理学抑制剂增强177 Lu-octreotate对这两种类型的NET细胞的2D单层和3D球体模型的细胞毒性作用。PARPi通过增强177 Lu-奥曲酸诱导的细胞周期停滞和细胞死亡来介导这种效应。因此，PARPi的使用可以提供用于改善NET的177 Lu-奥曲肽PRRT的治疗功效的新选择。
For patients with inoperable neuroendocrine tumors (NETs) expressing somatostatin receptors, peptide receptor radionuclide therapy (PRRT) with 177Lu-[DOTA0-Tyr3]-octreotate (177Lu-octreotate) is one of the most promising targeted therapeutic options but it rarely achieves cure. Therefore, different approaches are being tested to increase the efficacy of 177Lu-octreotate PRRT in NET patients. Using the gastroenteropancreatic BON-1 and the bronchopulmonary NCI-H727 as NET cell models, here we report that pharmacological inhibitors of DNA repair-associated enzyme poly(ADP-ribose) polymerase-1 (PARPi) potentiate the cytotoxic effect of 177Lu-octreotate on 2D monolayer and 3D spheroid models of these two types of NET cells. PARPi mediates this effect by enhancing 177Lu-octreotate-induced cell cycle arrest and cell death. Thus, the use of PARPi may offer a novel option for improving the therapeutic efficacy of 177Lu-octreotate PRRT of NETs.