Rapamycin inhibits proliferation and migration of hepatoma cells in vitro.
BACKGROUND
Systemic immunosuppression represents the major factor for cancer recurrence after orthotopic liver transplantation for hepatocellular carcinoma (HCC). Rapamycin is an immunosuppressant with unique antitumoral properties. Although rapamycin has been successfully used in HCC patients after liver transplantation, the detailed mechanisms of rapamycin action on tumor cells are poorly understood.


METHODS
Two HCC cell lines (PLC5 and HuH7) were used to evaluate the effect of rapamycin. Tumor cell proliferation was analyzed using cell counting and BrdU incorporation assay. Expression of phosphorylated Akt was studied using enzyme linked immunosorbent assay. Digital time-lapse microscopy was utilized to measure tumor cell migration in vitro.


RESULTS
Rapamycin induced a strongly dose-dependent inhibition of tumor cell proliferation in both HCC cell lines. Additionally, rapamycin inhibited activation of Akt phosphorylation and tumor cell migration after prolonged treatment.


CONCLUSIONS
Rapamycin suppresses tumor progression due to inhibition of phosphorylated Akt, cell proliferation, and migration. The data of the present study strengthen clinical implications of rapamycin after liver transplantation with HCC.
Shirouzu
Yasumasa
Y
Department of Surgery, University of Heidelberg, Heidelberg, Germany. shirouzu@fc.kuh.kumamoto-u.ac.jp <shirouzu@fc.kuh.kumamoto-u.ac.jp>
Ryschich
Eduard
E
Salnikova
Olga
O
Kerkadze
Vachtang
V
Schmidt
Jan
J
Engelmann
Guido
G
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000503:physiopathology; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008113:Liver Neoplasms / Q000473:pathology* / Q000503:physiopathology; D020123:Sirolimus / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D007166:Immunosuppressive Agents; D020123:Sirolimus