[Effects of Rapamycin on angiogenesis and tumor progression in human hepatocellular carcinoma implantation mice].
OBJECTIVE
To study the effects of Rapamycin (RPM) on angiogenesis and tumor progression in human hepatocellular carcinoma (HCC) implantation mice.


METHODS
Tumor tissues of HCC were implanted into the liver of nude mice. Then, nude mice were treated with RPM and cyclosporine A (CsA). Real-time PCR was used to detect the mRNA expression of vascular endothelial growth factor (VEGF). Immunohistochemical stain and image analysis were used to detect the protein expression of VEGF and proliferating cell nuclear antigen (PCNA) and microvessel density (MVD) was counted by endothelial cells immunostained by anti-CD34 antibody. The concentration of VEGF in the peripheral blood was detected by ELISA.


RESULTS
(1) The tumor weights were (372 +/- 35) mg, (769 +/- 39) mg and (751 +/- 42) mg in RPM, CsA and control group respectively. The tumor weight was significantly decreased in RPM group and no difference in CsA group compared with control group. (2) The expression of VEGF mRNA, VEGF and PCNA protein in tumor tissues and concentration of VEGF in the peripheral blood were remarkably down-regulated in RPM group compared with control group (P < 0.05) and were not remarkably different in CsA group from in control (P > 0.05).(3) Comparing with the control, the tumor MVD was remarkably decreased in RPM group (P < 0.05), and no difference in CsA group (P > 0.05).


CONCLUSIONS
RPM can inhibit angiogenesis and tumor progression of HCC by down-regulated the gene and protein expression of VEGF and inhibited the growth of tumor.
Zhang
Jian
J
Liver Transplantation Center, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
Li
Hua
H
Wang
Gen-shu
GS
Jiang
Nan
N
Yang
Yang
Y
Chen
Gui-hua
GH
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020123:Sirolimus / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D020123:Sirolimus