Ursodeoxycholic acid to inhibit the growth of hepatic metastases

Cancer can be resistant to apoptosis. If such cancers had apoptotic stimuli in their microenvironment, these stimuli might induce apoptosis in surrounding host cells. The majority of host cells at the peritumoral margins of liver metastases are undergoing apoptosis. Damage to the bile duct system may result in bile acid release, which may cause apoptosis in surrounding host cells. Metastatic cells may be releasing substances, such as transforming growth factor-beta 1 (TGF-beta 1), that cause apoptosis in surrounding host tissue. Ursodeoxycholic acid might inhibit the growth of hepatic metastases that are resistant to apoptotic stimuli such as bile acids and TGF-beta 1. Ursodeoxycholic acid decreases apoptosis caused by other bile acids and TGF-beta 1. Chemotherapy of hepatic metastases resistant to apoptosis might cause apoptosis more in peritumoral host cells than in cancer cells. Antiapoptotic therapy might be effective in cancer sensitive to apoptosis depending on its interactions with chemotherapy and tumor cells. (C) 2000 Harcourt Publishers Ltd.