Inhibition of lung metastasis by a calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), in mice bearing Lewis lung carcinoma.
The antimetastatic effect of calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) was examined in an experimental model of lung metastasis induced by Lewis lung carcinomas (3LL) in C57BL/6crSlc mice. 3LL cells were implanted into the footpad of the mice. Ten days later, the implanted primary tumors were surgically removed. Injection of W-7 i.v. after removal of the implanted primary tumor caused the greatest inhibition of development of lung metastases. The number of peritoneal macrophages, total cells and macrophages in the lung increased in mice treated with W-7. Binding of the third component of complement (C3) cleavage products (C3b) to the C3 receptor on peritoneal macrophages after i.v. injection of W-7 were enhanced, as shown by the fluorescent antibody technique. Lung metastases were inhibited by i.v. injection of peritoneal macrophages activated with W-7. A possible mechanism of inhibition of lung metastases by treatment with W-7 could be interpreted as due to C3 activation and macrophage activation. These findings raise the possibility that W-7 may have clinical value in the prevention of cancer metastasis.
Ito
H
H
Department of Pharmacology, Mie University School of Medicine, Japan.
Wang
J Z
JZ
Shimura
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D005260:Female; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D013449:Sulfonamides / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D002147:Calmodulin; D013449:Sulfonamides; C017967:W 7