Purohit Nupur K, Shah Rashmi G, Adant Samuel, Hoepfner Michael, Shah Girish M, Beauregard Jean-Mathieu
Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Quebec City, Canada.
Cancer Research Center, Université Laval, Quebec City, Canada.
Oncotarget. 2018 May 15;9(37):24693-24706. doi: 10.18632/oncotarget.25266.
For patients with inoperable neuroendocrine tumors (NETs) expressing somatostatin receptors, peptide receptor radionuclide therapy (PRRT) with Lu-[DOTA0-Tyr3]-octreotate (Lu-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 Lu-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 Lu-octreotate on 2D monolayer and 3D spheroid models of these two types of NET cells. PARPi mediates this effect by enhancing Lu-octreotate-induced cell cycle arrest and cell death. Thus, the use of PARPi may offer a novel option for improving the therapeutic efficacy of Lu-octreotate PRRT of NETs.
对于表达生长抑素受体的无法手术切除的神经内分泌肿瘤（NETs）患者，使用镥[DOTA0 - Tyr3] - 奥曲肽（镥 - 奥曲肽）进行肽受体放射性核素治疗（PRRT）是最有前景的靶向治疗选择之一，但很少能实现治愈。因此，正在测试不同的方法以提高镥 - 奥曲肽PRRT对NET患者的疗效。我们使用胃肠胰BON - 1和支气管肺NCI - H727作为NET细胞模型，在此报告DNA修复相关酶聚（ADP - 核糖）聚合酶 - 1（PARPi）的药理学抑制剂可增强镥 - 奥曲肽对这两种类型NET细胞的二维单层和三维球体模型的细胞毒性作用。PARPi通过增强镥 - 奥曲肽诱导的细胞周期停滞和细胞死亡来介导这种作用。因此，PARPi的使用可能为提高NETs的镥 - 奥曲肽PRRT的治疗效果提供一种新的选择。
