[Nanogold inhibits angiogenesis and growth of liver cancer: experiment with mice].
OBJECTIVE
To investigate the effects of nanogold in inhibition of angiogenesis and growth of liver cancer cells.


METHODS
Nanogold was co-incubated with VEGF165 and VDGF121 respectively. Atomic force microscopy (AFM) was used to observe the changes of the form of the particles. Human umbilical vascular endothelial cells (HUVEC) were serum-starved for 24 hours, then co-cultured with VEGF165 + nanogold or VEGF121 + nanogold for 24 h. ATM was used to observe the ultrastructure of the cells. Another HUVEC were serum-starved for 24 hours and then cultured with VEGF165 (10 microg/L) 100 microl + nanogold 125, 250, and 500 nmol/L 100 microl respectively for 5 min. Then Western blotting was used to detect the phosphorylation protein of phospholipase C (PLC)-gamma1 on VEGFR-2. Hepatocellular cancer cells of the line H22 were injected subcutaneously into the right armpit of 20 Balb/c nude mice. When the size of transplanted tumor reached about 8 mm, the mice were divided into 2 equal groups: experimental group undergoing injection of nanogold into the tumor once a day for 8 days, and control group injected with normal saline. On day 14 the mice were sacrificed with the liver tumors taken out to measure the size and weight. The microvascular density (MVD) of tumor was determined by immunohistochemical staining.


RESULTS
ATM showed that acted with VEGF165, the size of nanogold became over 30 nm. Treated with VEGF165 the HUVEC became larger with obvious pseudopodium. However, such changes were obviously milder in those HUVEC treated with nanogold + VEGF165. The PLC-gamma1 phosphorylation level VEGF receptor-2 was decreased along with the increase of the concentration of nanogold. The MVD of liver cancer tissue in the experimental group was 14.27 +/- 1.08, significantly lower than that of the control group [(23.52 +/- 1.36), P < 0.01]. The mean weight and volume of tumor of the experimental group were (1.39 +/- 0.08) g and (1.37 +/- 0.34) cm(3) respectively, both significantly lower than those of the control group [(2.47 +/- 0.15) g and (2.49 +/- 0.78) cm(3) respectively, both P < 0.05] with a tumor growth inhibition rate of 43.72%.


CONCLUSIONS
Nanogold significantly inhibits the angiogenesis and growth of liver cancer cells with the possible mechanism that nanogold inhibits the VEGF165-induced signaling.
Pan
Yun-Long
YL
Department of General Surgery, First Affiliated Hospital of Jinan University, Guangzhou 510632, China. tpanyl@jnu.edu.cn
Qiu
Si-Yuan
SY
Qin
Li
L
Cai
Ji-Ye
JY
Sun
Jia-Sheng
JS
D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006046:Gold / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000097:blood* / Q000473:pathology* / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A; D006046:Gold; D040301:Vascular Endothelial Growth Factor Receptor-2