Necrosis-inducing peptide has the beneficial effect on killing tumor cells through neuropilin (NRP-1) targeting.
Necrosis-inducing peptide has the beneficial effect on killing tumor cells through neuropilin (NRP-1) targeting.
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DOI：
10.18632/oncotarget.8719
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发表时间：
2016-05-31
期刊：
影响因子：
--
通讯作者：
Kim TH
中科院分区：
文献类型：
--
作者：
Kim JY;Han JH;Park G;Seo YW;Yun CW;Lee BC;Bae J;Moon AR;Kim TH
大多数抗癌药物的治疗效果取决于其诱导肿瘤的能力。以前，我们表明，含有线粒体靶向结构域（MTD）的肽中发现的Noxa，BH-3的Bcl-2家族的唯一蛋白，诱导坏死。在此，发现神经纤毛蛋白-1（NRP-1）靶向肽和MTD肽的融合肽，命名为肿瘤归巢基序17：MTD（TU 17：MTD），在体外诱导癌细胞坏死，并且当静脉内注射到携带皮下CT 26结肠直肠癌肿瘤的小鼠中时引起肿瘤消退。TU 17：MTD给药后，肿瘤组织内的坏死明显。TU 17：MTD通过靶向Neuropilin-1进入肿瘤细胞，可被抗NRP-1抗体阻断。TU 17：MTD对肿瘤消退的功效高于TU 17：D（KLAKLAK）2，TU 17：D（KLAKLAK）2是NRP-1靶向肽和促凋亡肽的融合肽。在全身给予TU 17：MTD后第1天，肿瘤组织内的坏死细胞死亡明显。皮下移植后，两周内和5天内的大小分别大幅减少，没有明显的副作用。总之，这些结果表明，促坏死肽MTD可能是开发靶向抗癌剂的替代方法。
The therapeutic efficacy of most anti-cancer drugs depends on their apoptosis-inducing abilities. Previously, we showed that a peptide containing the mitochondrial targeting domain (MTD) found in Noxa, a BH-3 only protein of Bcl-2 family, induces necrosis. Here, a fusion peptide of neuropilin-1 (NRP-1) targeting peptide and MTD peptide, designated tumor homing motif 17:MTD (TU17:MTD), was found to induce necrosis in cancer cells in vitro and to cause the regression of tumors when intravenously injected into mice bearing subcutaneous CT26 colorectal carcinoma tumors. The necrosis within tumor tissues was evident upon administering TU17:MTD. TU17:MTD penetrated into tumor cells by targeting to Neuropilin-1, which could be blocked by anti-NRP-1 antibody. The efficacy of TU17:MTD on tumor regression was higher than that of TU17:D(KLAKLAK)2, a fusion peptide of NRP-1 targeting peptide and a pro-apoptotic peptide. The necrotic cell death within tumor tissues was evident at day 1 after administering TU17:MTD systemically. Transplanted subcutaneous substantially reduced in size within two weeks and 5 days, respectively, with no apparent side effects. Together, these results propose that the pro-necrotic peptide MTD may present an alternative approach for development of targeted anti-cancer agents.
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