Applicability of anti-neovascular therapy to drug-resistant tumor: Suppression of drug-resistant P388 tumor growth with neovessel-targeted liposomal adriamycin
Applicability of anti-neovascular therapy to drug-resistant tumor: Suppression of drug-resistant P388 tumor growth with neovessel-targeted liposomal adriamycin
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DOI：
10.1016/j.ijpharm.2005.02.030
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发表时间：
2005-05-30
影响因子：
5.8
通讯作者：
Oku, N
中科院分区：
文献类型：
--
作者：
Shimizu, K;Asai, T;Oku, N
抗新生血管治疗是一种有效的抗血管生成化疗方法，它通过将细胞毒剂输送到新生血管内皮细胞来损伤新生血管，从而间接根除肿瘤细胞。我们先前曾报道，经五肽修饰的脂质体Ala-Pro-Arg-Pro-Gly(APRPG-Lip)和APRPG-Lip包裹阿霉素(APRPG-LipADM)能有效地抑制荷瘤小鼠的肿瘤生长。在本研究中，我们检测了荧光标记的APRPG-LipADM以及TUNEL染色的细胞在从结肠癌26 NL-17荷瘤小鼠的实际肿瘤标本中的拓扑分布。荧光标记的APRPG-Lip主要定位于血管样结构，部分血管样结构也被CD31抗体染色。此外，TUNEL染色的细胞共定位于相同的结构。这些结果表明，APRPG-LipADM与血管生成的内皮细胞结合并诱导其凋亡。我们还研究了APRPG-LipADM抗新生血管治疗对耐ADM的P388实体瘤的适用性。结果，APRPG-LipADM显著抑制了携带ADM耐药肿瘤的小鼠的肿瘤生长。这些结果表明，APRPG-LipADM适用于包括耐药肿瘤在内的各种肿瘤，因为它以血管生成的内皮细胞为靶细胞，而不是肿瘤细胞，并通过破坏新生血管来清除肿瘤细胞。(C)2005 Elsevier B.V.保留所有权利。
Anti-neovascular therapy, one of the effective anti-angiogenic chemotherapy, damages new blood vessels by cytotoxic agents delivered to angiogenic endothelial cells and results in indirect eradication of tumor cells. We previously reported that liposomes-modified with a pentapeptide, Ala-Pro-Arg-Pro-Gly (APRPG-Lip) horning to angiogenic site, highly accumulated in tumor tissue, and APRPG-Lip encapsulating adriamycin (APRPG-LipADM) effectively suppressed tumor growth in tumor-bearing mice. In the present study, we examined the topological distribution of fluorescence-labeled APRPG-LipADM as well as TUNEL-stained cells in an actual tumor specimen obtained from Colon 26 NL-17 carcinoma-bearing mice. The fluorescence-labeled APRPG-Lip dominantly localized to vessel-like structure: A part of which was also stained with anti-CD31 antibody. Furthermore, TUNEL-stained cells were co-localized to the same structure. These data indicated that APRPG-LipADM bound to angiogenic endothelial cells and induced apoptosis of them. We also investigated the applicability of anti-neovascular therapy using APRPG-LipADM to ADM-resistant P388 solid tumor. As a result, APRPG-LipADM significantly suppressed tumor growth in mice bearing the ADM-resistant tumor. These data suggest that APRPG-LipADM is applicable to various kinds of tumor including drug-resistant tumor since it targets angiogenic endothelial cells instead of tumor cells, and eradicates tumor cells through damaging the neovessels. (C) 2005 Elsevier B.V. All rights reserved.