[Inhibitory effect of angiogenesis inhibitor YH-16 in combination with 5-FU on liver metastasis of colorectal cancer].
OBJECTIVE
To study the effect of angiogenesis inhibitor YH-16 in combination with 5-FU on liver metastasis of colorectal cancer.


METHODS
In vitro, the inhibitory effects of YH-16 and 5-FU on the growth of vascular endothelial cells and colorectal cancer cells were examined by MTT assay. In vivo, colorectal cancer cells were transplanted into BALB/c mice, and the mice were divided into six groups randomly:control group, low-dose YH-16 group, middle-dose YH-16 group, high-dose YH-16 group, 5-FU group and combination group. The number of liver metastases, the size of primary tumor and the toxicity were examined after 2 weeks postoperatively. The expression of vascular endothelial growth factor (VEGF) in liver metastases was detected by immunohistochemistry, and tumor microvessel density (MVD) was measured by immunostaining with CD34 and factor VIII (monoclonal antibodies.


RESULTS
In vitro, YH-16 inhibited the growth of colon cancer cells and vascular endothelial cells, with the IC50 at (2.16+/-0.28) microg/ml and (0.64+/-0.10) microg/ml respectively. In vivo high-dose YH-16 and 5-FU had a remarkable inhibitory effect on liver metastasis, and the combination group showed significant enhancement on this effect (P< 0.05). The combination group and 5-FU group could inhibit the growth of primary tumor, but not found in YH-16 group. The toxicity of YH-16 was lower than that of 5-FU (P< 0.05), and the difference was not found in the toxicity between combination group and 5-FU group (P > 0.05). Expression of VEGF in liver metastases was clearly inhibited by YH-16 in combination with 5-FU or 5-FU alone compared to the control group, and MVD in middle-dose and high-dose YH-16 group, 5-FU group and combination group was lower than that in control group (P< 0.05).


CONCLUSIONS
The angiogenesis inhibitor YH-16 can inhibit liver metastasis of colorectal cancer through inhibiting the growth of vascular endothelial cells. YH-16 in combination with 5-FU has additive effect on inhibitory activity against liver metastasis.
Zhou
Zhi-wei
ZW
Department of Abdominal, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China. zhouzhiw@pub.guangzhou.gd.cn
Wan
De-sen
DS
Wang
Guo-qiang
GQ
Ren
Jing-qing
JQ
Lu
Zhen-hai
ZH
Tang
Shao-xian
SX
Ye
Yan-li
YL
Chen
Gong
G
Lin
Su-xia
SX
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000517:prevention & control* / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D005472:Fluorouracil