The cytotoxic effects of bile acids in crude bile on human pancreatic cancer cell lines

Pancreatic cancer frequently causes extrahepatic cholestasis. To identify the direct effects of bile acids in jaundiced serum on pancreatic cancer, the proliferation of PANC-1 and MIA PaCa-2 cells as well as the ultrastructural alteration of PANC-1 cells cultured in crude bile modified media were studied. The growth of these cells in the RPMI-1640 media with or without 1%, 2%, and 4% of the refined crude bile was assessed after 48 and 96 h of incubation. The ultrastructure of PANC-1 cells was investigated by scanning and transmission electron microscopy after 24 and 48 h of incubation. The proliferation of both cell lines in the bile-treated media was greatly inhibited. The inhibitory rates of bile on PANC-1 ranged from 24.1% ± 3.3% to 66.9% ± 6.6% (P < 0.01) and those on MIA PaCa-2 ranged from 16.7% ± 3.8% to 50.7% ± 5.5%. (P < 0.01). When the bile-added media were replaced, the cells were able to restore their proliferating ability. The PANC-1 cells incubated in the bile-supplied media indicated that the mirovilli, mitochondria, and other organelles had thus been injured. These results suggest that bile acids appear to inhibit the proliferation of PANC-1 and MIA PaCa-2 cells, and the probable inhibitory mechanism is mainly considered to be due to the cytotoxicity of such bile acids. Received: November 2, 1999 / Accepted: May 30, 2000