[The effect of VEGF antisense oligonucleotides combined with low molecular weight heparin on the growth and metastasis of mice Lewis lung cancer].
OBJECTIVE
To investigate the inhibitory effect of vascular endothelial growth factor (VEGF) antisense oligonucleotides or/and dalteparin sodium (fragmin) on tumor growth and metastasis of mice Lewis lung cancer.


METHODS
40 mice with Lewis lung cancer were randomizedly divided into five groups: control group, VEGF antisense oligonucleotides (ASODN) group, VEGF mismatch sense oligonucleotides (MSODN) group, low molecular weight heparin (LMWH) group, and combined group. Sodium chloride, VEGF-ASODN, VEGF -MSODN, fragmin, and VEGF-ASODN plus fragmin were given respectively (once every two days, 15 times altogether). The volume and weight of subcutaneous tumors were measured, and the rates of lung metastasis were detected by HE staining. The microvessel density (MVD) in tumor mass were measured by immunohistochemistry staining. VEGF protein level in tumor tissue were detected by Western blot assay.


RESULTS
After treatment, the tumor growth inhibitory rates were 47.34%, 27.31% and 59.03%, and the rates of lung metastasis were 37.5%, 37.5% and 25% in ASODN, LMWH, and the combined group, respectively. Tumor MVD and VEGF protein expression of the above three groups were lower than those of the control group. There was a significant difference in regard to the tumor growth inhibitory rates and MVD between the above three treated groups and the control group as well as the MSODN group (P < 0.05).


CONCLUSIONS
VEGF-ASODN and fragmin may down-regulate VEGF gene expression and inhibit angiogenesis, Combined use of fragmin can enhance anti- tumor effect of VEGF-ASODN.
Zhang
Yu-hui
YH
Beijing Institute of Respiratory Disease, Beijing Chaoyang Hospital Affiliated to Capital University of Medical Science, Beijing 100020, China.
Wang
Chen
C
Pang
Bao-sen
BS
Zhai
Zhen-guo
ZG
Weng
Xin-zhi
XZ