Anti-metastatic effects of liposomal gemcitabine in a human orthotopic LNCaP prostate cancer xenograft model
Anti-metastatic effects of liposomal gemcitabine in a human orthotopic LNCaP prostate cancer xenograft model
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DOI：
10.1007/s10585-009-9288-1
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发表时间：
2009-12-01
影响因子：
4
通讯作者：
Massing, Ulrich
中科院分区：
文献类型：
--
作者：
Jantscheff, Peter;Ziroli, Vittorio;Massing, Ulrich
前列腺癌（PCa）的致死性结局主要是由于转移性扩散，而不是原发性肿瘤负荷。在这里，我们监测原位荧光素酶/GFP表达LNCaP PCa异种移植模型在SCID小鼠的生长和转移扩散的体内成像和组织匀浆的体外荧光素酶测定。虽然转移性扩散通常显示与原发肿瘤体积显著相关，但各种组织对转移性侵袭的易感性在受影响动物的数量以及个体组织的绝对转移负荷方面不同。使用这种异种移植模型，我们发现用脂质体吉西他滨（GemLip）治疗可以抑制原发性肿瘤的生长。（83.9 +/- A 6.4%; P = 0.009）以及淋巴结转移负荷（95.6 +/- A 24.0%; P = 0.047），肺（86.5 +/- A 10.5%; P = 0.015），肾脏（88.4 +/- A 9.2%; P = 0.045）和胃（79.5 +/- A 6.6%; P = 0.036）已经处于非常低的有效浓度（8 mg/kg），与常规吉西他滨（360 mg/kg）相比。我们的数据表明，这种原位LNCaP异种移植PCa模型似乎反映了临床情况，其特征在于在诊断时，前列腺肿瘤具有生物学异质性，因此，它是研究新的抗转移治疗的有用模型。
Fatal outcomes of prostate carcinoma (PCa) mostly result from metastatic spread rather than from primary tumor burden. Here, we monitored growth and metastatic spread of an orthotopic luciferase/GFP-expressing LNCaP PCa xenograft model in SCID mice by in vivo imaging and in vitro luciferase assay of tissues homogenates. Although the metastatic spread generally shows a significant correlation to primary tumor volumes, the susceptibility of various tissues to metastatic invasion was different in the number of affected animals as well as in absolute metastatic burden in the individual tissues. Using this xenograft model we showed that treatment with liposomal gemcitabine (GemLip) inhibited growth of the primary tumors (83.9 +/- A 6.4%; P = 0.009) as well as metastatic burden in lymph nodes (95.6 +/- A 24.0%; P = 0.047), lung (86.5 +/- A 10.5%; P = 0.015), kidney (88.4 +/- A 9.2%; P = 0.045) and stomach (79.5 +/- A 6.6%; P = 0.036) already at very low efficient concentrations (8 mg/kg) as compared to conventional gemcitabine (360 mg/kg). Our data show that this orthotopic LNCaP xenograft PCa model seems to reflect the clinical situation characterized by the fact that at time of diagnosis, prostate neoplasms are biologically heterogeneous and thus, it is a useful model to investigate new anti-metastatic therapies.