Antitumor effect of kigamicin D on mouse tumor models
Antitumor effect of kigamicin D on mouse tumor models
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DOI：
10.1038/ja.2006.29
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发表时间：
2006-04-01
影响因子：
3.3
通讯作者：
Kunimoto, S
中科院分区：
文献类型：
--
作者：
Masuda, T;Ohba, S;Kunimoto, S
Kigamicin D是一种新型抗癌药物，使用靶向癌细胞对营养饥饿的耐受性的新筛选策略进行鉴定[1，2]。先前描述了口服给予庆大霉素D在胰腺肿瘤的人肿瘤异种移植模型中显示出强烈的抗肿瘤作用[2]。本文描述了庆大霉素D在营养缺乏条件下对正常人细胞如肺成纤维细胞和前列腺基质细胞显示出与对癌细胞相同的选择性细胞毒性。在背气囊试验中，Kigamicin D抑制肿瘤细胞诱导的血管生成。在这些结果的基础上，我们测试了其他人肿瘤异种移植模型和可移植的同基因肿瘤模型，以确定庆大霉素D的活性谱。各种癌症。Kigamicin D对LX-1和DMS-273肺癌有较弱的抗肿瘤作用，但对DLD-1结肠癌无作用。当针对同源肿瘤进行测试时，庆大霉素D对结肠26显示出弱的抗肿瘤作用，但在宽剂量水平下显示出对IMC癌的肿瘤生长的增强。除了胰腺肿瘤和小鼠同源肿瘤外，Kigamicin D对人类异种移植肿瘤没有显示出良好的抗肿瘤活性。我们发现庆大霉素D对胰腺癌有很好的特异性抗肿瘤作用。令人惊讶的是，高剂量的庆大霉素D使IMC癌的肿瘤生长增加了200%以上。这一现象表明，庆大霉素D可能会引起一些免疫反应的肿瘤。
Kigamicin D is a novel anticancer agent that was identified using a new screening strategy that targets the tolerance of cancer cells to nutrient starvation [1, 2]. Oral administration of kigamicin D was previously described to show a strong antitumor effect in human tumor xenograft models of pancreatic tumors [2]. In this paper we describe that kigamicin D shows the same selective cytotoxicity against normal human cells such as lung fibroblast and prostate stromal cells under nutrient starved condition as against cancer cells. Kigamicin D inhibited tumor cell-induced angiogenesis in a dorsal air sac assay. On the basis of these results we tested other human tumor xenograft models and transplantable syngeneic tumor models in order to determine the spectrum of activity of kigamicin D against. various cancers. Kigamicin D showed a weak antitumor effect against LX-1 and DMS-273 lung cancers, but had no effect on DLD-1 colon cancers. When tested against syngeneic tumors, kigamicin D showed a weak antitumor effect against colon26, but showed augmentation of tumor growth on IMC carcinoma at a broad dosage level. Kigamicin D does not show good antitumor activity against human xenograft tumors except pancreatic tumors and murine syngeneic tumors. We found that kigamicin D has excellent antitumor effect specific to pancreatic cancers. Surprisingly, high dosage of kigamicin D increased tumor growth of IMC carcinoma by than 200%. The phenomenon suggests that kigamicin D may cause some immunological response to the tumor.