Antisense oligonucleotide of hypoxia-inducible factor-1alpha suppresses growth and tumorigenicity of lung cancer cells A549.
To study the role and mechanisms of hypoxia-inducible factor-1alpha (HIF-1alpha) on the growth and tumorigenicity of lung cancer cells A549, the antisense oligonucleotide of HIF-1alpha was transfected to A549 cells. The effect of the antisense oligonucleotide on tumor growth in vitro and in vivo was evaluated by the growth rate suppression of A549 cells and subcutaneous implanted tumor in nude mice, and the effect on tumorigenicity was evaluated by the expression inhibition of angiogenic factors, the microvessel density (MVD) and vascular endothelial growth factor (VEGF) protein expression which were detected by immohistochemistry and western blot respectively. This study revealed that in vitro the growth rate of antisense oligonucleotide group was significantly decreased as compared with that of control group, sense oligonucleotide group and false-sense oligonucleotide group; in vivo the weight of implanted tumors in nude mice of antisense oligonucleotide group was 1.51 +/- 0.40 g, which was significantly lower than that of control group (2.79 +/- 0.33 g), sense oligonucleotide group (2.81 +/- 0.45 g) and false-sense oligonucleotide group (2.89 +/- 0.39 g) and the inhibitory rate was 47%. Both MVD and VEGF protein expression were significantly inhibited in antisense oligonucleotide group compared with those in other groups. These results indicated that antisense oligonucleotide of HIF-1alpha could inhibit lung cancer cells A549 growth in vitro and in vivo, and the mechanism may be due to the inhibition of vascular growth and VEGF protein expression.
Zhang
Wanguang
W
Hepatic Surgery Center Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Zhang
Huilan
H
Xing
Lihua
L
D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D005260:Female; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D016376:Oligonucleotides, Antisense / Q000235:genetics*; D011897:Random Allocation; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016376:Oligonucleotides, Antisense; D042461:Vascular Endothelial Growth Factor A