Evaluation of the anti-tumor and anti-angiogenic effect of paclitaxel and thalidomide on the xenotransplanted oral squamous cell carcinoma
Evaluation of the anti-tumor and anti-angiogenic effect of paclitaxel and thalidomide on the xenotransplanted oral squamous cell carcinoma
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DOI：
10.1016/s0304-3835(00)00701-1
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发表时间：
2001-02-26
期刊：
影响因子：
9.7
通讯作者：
Kim, MJ
中科院分区：
文献类型：
--
作者：
Myoung, H;Hong, SD;Kim, MJ
血管生成是肿瘤生长和侵袭的重要过程。然而，抗血管生成作用能否成为口腔癌的主要治疗策略尚不确定。本研究旨在探讨已知的血管生成专利抑制剂沙利度胺和紫杉醇是否对口腔鳞状细胞癌（OSCC）异种移植裸鼠的生长有抑制作用，以及抗血管生成是否可以作为口腔癌的主要治疗策略。将人OSCC细胞系KB皮下接种32只裸鼠，每3天测定肿瘤体积。当肿瘤体积达到300-500 mm(3)时，给予沙利度胺（200 mg/kg）和紫杉醇（13 mg/kg），观察肿瘤体积变化。给药后第30天切除的肿瘤块冷冻，用血管内皮生长因子（VEGF）和CD31进行免疫组化处理，并进行实时逆转录聚合酶链反应（RT-PCR）。我们评估了VEGF的表达及其mRNA和CD31的表达与血管密度的关系。紫杉醇对移植人OSCC的生长有抑制作用，降低VEGF、CD31和VEGF mRNA的免疫组化表达（P < 0.01）。沙利度胺可显著降低VEGF表达（P < 0.01）、CD31表达（P < 0.01）及VEGF mRNA表达（P < 0.05），但对肿瘤生长无显著抑制作用。这些结果表明，人类OSCC的生长并不仅仅依赖于vegf诱导的血管生成，单独的抗血管生成治疗不太可能对OSCC的治疗有效，但可能被视为辅助化疗策略。(C) 2001爱思唯尔科学爱尔兰有限公司版权所有。
Angiogenesis is an essential process for the growth and invasion of cancer. However, it is uncertain that anti-angiogenic effects can be a major treatment strategy of oral cancer. The aim of this study was to investigate whether thalidomide and paclitaxel, which are known to be patent inhibitors of angiogenesis, have inhibitory effects on the growth of oral squamous cell carcinoma (OSCC) xenotransplanted into nude mice and whether anti-angiogenesis can be included as a major treatment strategy of oral cancer. After human OSCC cell line, KB, was subcutaneously inoculated into 32 nude mice, the volume of tumor was measured every 3 days. When the tumor mass reached 300-500 mm(3), thalidomide (200 mg/kg) and paclitaxel (13 mg/kg) were administered into the animals and tumor volume change was checked. The excised tumor masses on the 30th day after administration were frozen and processed for immunohistochemistry using vascular endothelial growth factor (VEGF) and CD31, and for real-time reverse transcription-polymerase chain reaction (RT-PCR). We evaluated VEGF expression and the expression of its mRNA and CD31 for vessel density. Paclitaxel showed an inhibitory effect on the growth of transplanted human OSCC and reduced the immunohistochemical expression of VEGF and CD31 and VEGF mRNA (P < 0.01). Thalidomide also lowered remarkably VEGF expression (P < 0.01) and CD31 (P < 0.01) as well as VEGF mRNA (P < 0.05), but it did not show statistically significant inhibitory effect on the tumor growth. These results suggest that the growth of human OSCC is not simply dependent on VEGF-induced angiogenesis and that anti-angiogenic therapy alone is not likely to be effective for the treatment of OSCC, but might be regarded as adjuvant chemotherapeutic strategy. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.