title: Anti-angiotensin and hypoglycemic treatments suppress liver metastasis of colon cancer cells.
abstract: 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.
authors.affiliation: Department of Molecular Pathology, Nara Medical University, Kashihara, Japan.
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ohmori
authors.forename: Takasumi
authors.initials: T
authors.lastname: Shimomoto
authors.forename: Kiyomu
authors.initials: K
authors.lastname: Fujii
authors.forename: Tomonori
authors.initials: T
authors.lastname: Sasahira
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Chihara
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kuniyasu
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology*; D000809:Angiotensins / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D015151:Immunoblotting; D007328:Insulin / Q000494:pharmacology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D057911:Angiotensin Receptor Antagonists; D000809:Angiotensins; D007004:Hypoglycemic Agents; D007328:Insulin