[Effects of sirolimus on the growth of transplanted hepatocellular carcinoma].
OBJECTIVE
To study the effects of sirolimus (SRL) on the growth of transplanted human hepatocellular carcinoma (HCC) in nude mice.


METHODS
HepG2 cells were Implanted into the liver of nude mice. The implanted mice were then treated with SRL and tacrolimus (FK506). The expression of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) was detected by immunohistology, microvessel density (MVD) was counted by immunostaining with anti-CD34 antibody for endothelial cells. Tumor apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay.


RESULTS
The tumor weight was (352+/-38) mg, (683+/-53) mg and (675+/-45) mg in SRL, FK506 and control group respectively. The tumor weight was significantly decreased in SRL group (P < 0.01), and there was no difference between FK506 group and control group. The expression of VEGF and PCNA protein was remarkably down-regulated in SRL group compared to control group (P < 0.05), and it was not significantly different between FK506 group and control group (P > 0.05). Compared to the control group, MVD was significanly decreased in SRL group, and the apoptosis index of tumor cell was significantly higher in SRL group (P < 0.01).


CONCLUSIONS
SRL inhibits transplanted HCC tumor growth by reducing tumor angiogenesis, inhibiting tumor proliferation and inducing tumor apoptosis.
Zhang
Jian
J
Liver Transplantation Center, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. zhangjian629@sina.com
Li
Hua
H
Wang
Gen-shu
GS
Jiang
Nan
N
Yang
Yang
Y
Chen
Gui-hua
GH
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000098:blood supply / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D020123:Sirolimus / Q000008:administration & dosage / Q000494:pharmacology*; D016559:Tacrolimus / Q000008:administration & dosage / Q000494:pharmacology; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D018809:Proliferating Cell Nuclear Antigen; D042461:Vascular Endothelial Growth Factor A; D020123:Sirolimus; D016559:Tacrolimus