Anti-Angiotensin and Hypoglycemic Treatments Suppress Liver Metastasis of Colon Cancer Cells
Anti-Angiotensin and Hypoglycemic Treatments Suppress Liver Metastasis of Colon Cancer Cells
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DOI：
10.1159/000330169
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发表时间：
2011-01-01
期刊：
影响因子：
5
通讯作者：
Kuniyasu, Hiroki
中科院分区：
文献类型：
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作者：
Luo, Yi;Ohmori, Hitoshi;Kuniyasu, Hiroki
以CT26小鼠结肠癌细胞为研究对象，研究糖尿病对肝转移的影响。CT26细胞从血管紧张素原产生血管紧张素(A)-I和A-II；这种产生被肾素和糜酶抑制剂所抑制。随着培养液中葡萄糖浓度的增加，肾素的表达和A-II的产生增加。在给予高热量饮食的链脲佐菌素诱导的BALB/c小鼠糖尿病模型中，血糖水平升高，并与CT26肝转移瘤的大小和数量增加有关。在这个糖尿病小鼠模型中，CT26细胞的肝转移可以通过使用糜酶抑制剂、肾素抑制剂和A-II受体阻滞剂的抗血管紧张素治疗来抑制。此外，同时降糖和抗血管紧张素治疗显示出协同抑制CT26细胞肝转移的作用。这些结果表明，血管紧张素激活能力与糖尿病相关，可促进结肠癌的肝转移。因此，抗血管紧张素和降血糖药物的治疗可能与糖尿病结肠癌患者的基线管理有关，以防止肝转移。这一方案需要在临床环境中进行检查。版权所有(C)2011 S.Karger AG，巴塞尔
The effect of diabetic conditions on liver metastasis was examined using CT26 mouse colon cancer cells. CT26 cells produced angiotensin (A)-I and A-II from angiotensinogen; the production was abrogated by inhibitors of renin and chymase. Renin expression and A-II production increased with an increase in the concentration of glucose in the medium. In a streptozotocin-induced BALB/c mouse diabetes model that was fed a high-calorie diet, the blood sugar level increased and was associated with an increasing size and number of CT26 liver metastases. In this diabetic mouse model, liver metastasis of CT26 cells was suppressed by anti-angiotensin treatment with a chymase inhibitor, a renin inhibitor, and an A-II receptor blocker. Moreover, concurrent hypoglycemic and anti-angiotensin treatments showed a synergistic inhibitory effect on CT26 cell liver metastasis. These results suggest that angiotensin activation ability associated with diabetic conditions enhances liver metastasis of colon cancer. Therefore, treatment with anti-angiotensin and hypoglycemic agents might be relevant for baseline management of colon cancer patients with the diabetic condition for the prevention of liver metastasis. This scheme needs to be examined in a clinical setting. Copyright (C) 2011 S. Karger AG, Basel