Paclitaxel encapsulated in cationic liposomes: A new option for neovascular targeting for the treatment of prostate cancer

Paclitaxel encapsulated in cationic liposomes: A new option for neovascular targeting for the treatment of prostate cancer
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DOI:
10.3892/or_00000440
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发表时间:
2009-08-01
期刊:
影响因子:
4.2
通讯作者:
Michel, Maurice Stephan
Michel, Maurice Stephan
中科院分区:
医学3区
文献类型:
--
作者:
Bode, Christian;Trojan, Lutz;Michel, Maurice Stephan

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新生血管靶向是治疗前列腺癌(PCa)的既定方法。阳离子脂质体由于其外细胞膜的负电荷而被未成熟的血管内皮细胞吸收。我们的目的是评价紫杉醇阳离子脂质体包封治疗前列腺癌的抗肿瘤疗效。通过将10(6)个MatLU肿瘤细胞皮下注射到21只雄性Copenhagen大鼠的右后腿中产生肿瘤。肿瘤生长后,在第12、14、16和19天,通过静脉内输注5%葡萄糖(GI)、紫杉醇(Pax)、阳离子脂质体(CL)或包封在阳离子脂质体中的紫杉醇(EndoTAG-1)来治疗动物。在肿瘤接种后第12天开始治疗,平均肿瘤体积为0.31 ± 0.13 mm(3)。在治疗的最后一天,用EndoTAG-1治疗的动物具有显著最低的肿瘤体积,为2.49 +/- 0.84 cm(3)vs. Pax(5.59 +/- 0.45 cm(3))vs. CL(3.87 +/- 1.25 cm(3))vs. GL(5.17 +/- 1.70 cm(3))。MVD的定量显示EndoTAG-1处理的肿瘤的最低计数(11.78 +/- 2.68血管/mm(2)),其次是GI(15.64 +/- 6.68血管/mm(2))、Pax(18.22 +/- 9.50血管/mm(3))和CL(40.9 +/- 32.8血管/mm(3))。数据证实,与常规治疗相比,EndoTAG-1的新生血管靶向治疗是一种有前途的治疗PCa的新方法,可减少原发性肿瘤质量,并显示出抑制血管生成的益处。
Neovascular targeting is an established approach for the therapy of prostate cancer (PCa). Cationic liposomes have been shown to be absorbed by immature vascular endothelial cells due to negative electric charge of their outer cell membrane. We aimed to evaluate the antitumoural efficacy of paclitaxel encapsulated in cationic liposomes for the treatment of PCa. Tumours were generated by subcutaneous injection of 10(6) MatLU tumour cells into the right hind leg of 21 male Copenhagen rats. After tumour growth, the animals were treated by an i.v. infusion with either 5% glucose (Gl), paclitaxel (Pax), cationic liposomes (CL) or paclitaxel encapsulated in cationic liposomes (EndoTAG-1) on days 12, 14, 16 and 19. Treatment was initiated on day 12 after tumour inoculation at mean tumour volumes of 0.31 0.13 mm(3). On the last day of treatment, animals treated with EndoTAG-1 had the significantly lowest tumour volumes with 2.49 +/- 0.84 cm(3) vs. Pax (5.59 +/- 0.45 cm(3)) vs. CL (3.87 +/- 1.25 cm(3)) vs. GL (5.17 +/- 1.70 cm(3)). The quantification of MVD showed the lowest count for EndoTAG-1-treated tumours (11.78 +/- 2.68 vessels/mm(2)) followed by Gl (15.64 +/- 6.68 vessels/mm(2)), Pax (18.22 +/- 9.50 vessels/mm(3)) and CL (40.9 +/- 32.8 vessels/mm(3)). The data confirm that neovascular targeting with EndoTAG-1 is a promising new method for the treatment of PCa by reducing the primary tumour mass and demonstrating benefits in the suppression of angiogenesis in comparison with the conventional treatment.