Tao H Q, Lin Y Z, Yin H R, Gu Q L, Zhu Z G, Yao M
Hou-Quan Tao, Yan-Zhen Lin, Hao-Ran Yin, Qin-Long Gu, Zheng-Gang Zhu, Ming Yao, Department of Surgery, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
World J Gastroenterol. 1997 Sep 15;3(3):153-5. doi: 10.3748/wjg.v3.i3.153.
To elucidate the effect of angiogenesis inhibitor, Linomide, on tumor growth and metastasis in nude mice implanted with human gastric cancer.
A metastatic model of gastric cancer was established using orthotopic implantation of histologically intact tumor tissues into the gastric wall of nude mice. Linomide (0, 80, 160 mg·kg(-1)) was given p.o. every day after the implantation, and the mice were sacrificed after 10 wk to detect tumor size and metastasis. The microvessel counts were measured by immunohistochemical staining using a monoclonal antibody against Human Factor VIII related antigen.
Linomide treatment significantly decreased the size of the implanted tumors (control group: 1.36 ± 0.81 cm(3) vs Linomide treated group: 0.84 ± 0.51 cm(3) and 0.62 ± 0.35 cm(3), P < 0.05 and 0.01, respectively). Additionally, an antimetastatic effect of Linomide was clearly demonstrated in a dose dependent manner: mice given 80 mg·kg(-1) Linomide developed liver metastasis in 4 of 10 cases, mice given 160 mg/kg developed metastasis in only 1 of 10 mice, while it developed in 19 of 28 mice of the control group (P < 0.05 and 0.01, respectively). The number of metastatic foci was also significantly less in the treated group. Furthermore, the microvessel counts in tumors of treated mice was reduced by 33%-42% as compared with the control tumors (P < 0.01).
Linomide has a strong inhibitory activity against in vivo tumor growth and metastasis of gastric cancer, effectively suppressing the growth of the primary tumor, preventing liver metastasis, and attenuating the rate of neovascularization.
阐明血管生成抑制剂利诺胺对人胃癌裸鼠移植瘤生长及转移的影响。
采用将组织学完整的肿瘤组织原位植入裸鼠胃壁的方法建立胃癌转移模型。植入后每天经口给予利诺胺（0、80、160mg·kg⁻¹），10周后处死小鼠，检测肿瘤大小及转移情况。采用抗人因子VIII相关抗原单克隆抗体免疫组化染色法测定微血管计数。
利诺胺治疗显著减小了移植瘤的大小（对照组：1.36±0.81cm³，利诺胺治疗组：0.84±0.51cm³和0.62±0.35cm³，P分别<0.05和0.01）。此外，利诺胺的抗转移作用呈明显的剂量依赖性：给予80mg·kg⁻¹利诺胺的小鼠10只中有4只发生肝转移，给予160mg/kg的小鼠10只中仅1只发生转移，而对照组28只小鼠中有19只发生转移（P分别<0.05和0.01）。治疗组的转移灶数量也明显减少。此外，与对照肿瘤相比，治疗小鼠肿瘤中的微血管计数减少了33%-42%（P<0.01）。
利诺胺对胃癌体内肿瘤生长和转移具有强大的抑制活性，能有效抑制原发肿瘤生长，预防肝转移，并降低新生血管形成率。
