NM-3, an isocoumarin, increases the antitumor effects of radiotherapy without toxicity.-猫眼课题宝

DOI：

发表时间：

2000-12

期刊：

Cancer research

影响因子：

11.2

通讯作者：

中科院分区：

医学1区

文献类型：

作者：

Rabih M. Salloum;Nora Jaskowiak;H. Mauceri;S. Seetharam;Michael A. Beckett;A. Koons;Danielle M. Hari;Vinay K. Gupta;Corinne L. Reimer;Raghu Kalluri;Mitchell C. Posner;Samuel Hellman;Donald Kufe;Ralph R. Weichselbaum

我们研究了一种新的抗血管生成异香豆素，NM-3，作为一种辐射改性剂在体外和体内的影响。目前的研究表明，NM-3是细胞毒性的人脐静脉内皮细胞（HUVEC），但不刘易斯肺癌（LLC）细胞，也没有Seg-1，食管腺癌细胞，在克隆生存测定。当HUVEC培养物用NM-3与电离辐射（IR）组合处理时，观察到附加的细胞毒性。此外，NM-3和IR的组合抑制HUVEC迁移的程度大于单独的任一种治疗。还在肿瘤模型系统中评价了NM-3和IR治疗的效果。对携带LLC肿瘤的C57 BL/6雌性小鼠连续4天注射NM-3（25 mg/kg/天），并连续2天用IR（20戈伊）处理。NM-3和IR联合治疗与单独治疗相比显著降低了平均肿瘤体积。在接受NM-3/IR治疗的小鼠的LLC肿瘤中也观察到局部肿瘤控制的增加。当用NM-3（100 mg/kg/天，持续4天）和20戈伊（4个5戈伊分次）治疗携带Seg-1肿瘤异种移植物的无胸腺裸鼠时，与单独IR相比，在联合治疗（NM-3和IR）后观察到显著的肿瘤消退。重要的是，与单独IR相比，在联合治疗（NM-3和IR）后没有观察到全身或局部组织毒性的增加。NM-3的生物利用度和无毒特性表明，该药物的疗效应在临床放射治疗中进行测试。

We examined the effects of a new antiangiogenic isocoumarin, NM-3, as a radiation modifier in vitro and in vivo. The present studies demonstrate that NM-3 is cytotoxic to human umbilical vein endothelial cells (HUVECs) but not to Lewis lung carcinoma (LLC) cells nor Seg-1, esophageal adenocarcinoma cells, in clonogenic survival assays. When HUVEC cultures are treated with NM-3 combined with ionizing radiation (IR), additive cytotoxicity is observed. In addition, the combination of NM-3 and IR inhibits HUVEC migration to a greater extent than either treatment alone. The effects of treatment with NM-3 and IR were also evaluated in tumor model systems. C57BL/6 female mice bearing LLC tumors were given injections for 4 consecutive days with NM-3 (25 mg/kg/day) and treated with IR (20 Gy) for 2 consecutive days. Combined treatment with NM-3 and IR significantly reduced mean tumor volume compared with either treatment alone. An increase in local tumor control was also observed in LLC tumors in mice receiving NM-3/IR therapy. When athymic nude mice bearing Seg-1 tumor xenografts were treated with NM-3 (100 mg/kg/day for 4 days) and 20 Gy (four 5 Gy fractions), significant tumor regression was observed after combined treatment (NM-3 and IR) compared with IR alone. Importantly, no increase in systemic or local tissue toxicity was observed after combined treatment (NM-3 and IR) when compared with IR alone. The bioavailability and nontoxic profile of NM-3 suggests that the efficacy of this agent should be tested in clinical radiotherapy.

NM-3, an isocoumarin, increases the antitumor effects of radiotherapy without toxicity.

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