[Inhibitory effect of angiogenesis inhibitor YH-16 on liver metastases from colorectal cancer].
OBJECTIVE
YH-16, a new recombinant angiogenesis inhibitor, has demonstrated synergetic effects with chemotherapy in non-small-cell lung cancer treatment in stage II clinical trial. This study was to investigate the effect of YH-16 on liver metastases from colon cancer.


METHODS
Inhibitory concentration 50% (IC(50)) of YH-16 on vascular endothelial cells and colon cancer cell line CT26 was determined by MTT assay. Furthermore, the mouse mode of colon cancer liver metastases was established by inoculating CT26 cells into the subcapsule of spleen. 60 mice were randomly divided into four groups: control group (0 mg/kg), low-dose YH-16 group (0.40 mg/kg), medium-dose YH-16 group (0.75 mg/kg) and high-dose YH-16 group (1.5 mg/kg). The numbers of liver metastases were examined 2 weeks after drug injection. The expression of vascular endothelial growth factor (VEGF) was detected by immunohistochemical method in liver metastases, and tumor microvessel density (MVD) was measured by immunostaining using factor VIII monocolonal antibody.


RESULTS
Proliferation of CT26 and vascular endothelial cells was inhibited by YH-16, which the IC(50) was (2.16+/-0.28) microg/ml and (0.64+/-0.10) microg /ml, respectively. In vivo, the liver metastasis rates in control, low-dose, medium-dose and high-dose groups were 100%, 92.3%, 80% and 73.3%, respectively (P<0.05). However, YH-16 did not inhibit the growth of spleen tumors of which median volumes were 1.180 cm(3), 1.201 cm(3), 0.887 cm(3) and 0.781 cm(3), respectively (P>0.05). There was no difference of VEGF expression in liver metastases among the four groups. Moreover, MVD was 65.00+/-9.58, 58.15+/-8.81, 51.60+/-7.10 and 44.53+/-11.47 in the four groups. MVD in medium-dose and high-dose YH-16 groups was lower than that in control group and MVD was lower in high-dose group than that in medium-dose and low-dose groups (P<0.05).


CONCLUSIONS
Angiogenesis inhibitor YH-16 can inhibit liver metastases from colorectal cancer.
Zhou
Zhi-Wei
ZW
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong Province, 510060, P. R. China. zhouzhiw@pub.guangzhou.gd.cn
Wan
De-Sen
DS
Wang
Guo-Qiang
GQ
Ren
Jing-Qing
JQ
Lu
Zhen-Hai
ZH
Lin
Su-Xia
SX
Tang
Shao-Xian
SX
Ye
Yan-Li
YL
Chen
Gong
G
D000230:Adenocarcinoma / Q000473:pathology / Q000556:secondary; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D043169:Endostatins / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D020128:Inhibitory Concentration 50; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D055806:Microvessels / Q000473:pathology; D011897:Random Allocation; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D043169:Endostatins; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse