The Effect Of Hypoxia Inducible Factor 1 Alpha Antisense Oligonucleotides On Cell Proliferation Of Cervical Carcinoma

Background: Recently, as the researches of malignant neoplasm some author discovered that HIF-1αmay be the key translator-factor to adapt the hapoxia condition for most cells. HIF-1αalso can indirectly modulate the expression of VEGF that promote the development of the neoplasm. Normally, the neoplasm which develop fast more stoma and vessel but less connective tissue, the neoplasm which develop slow is converse. Without new vessels, the neoplasm whose diameter exceeds 1-2 mm or counts to 107 would grow no more, so inducing the new vessels is essential to the development, infiltration and metastasis of the neoplasm. The over-development of the neoplasm will cause to hypoxia. Then hypoxia stimulate more new vessels, this improves the development of neoplasm.Objective:To explore the inhibiting effect of hypoxia inducible factor 1 alpha antisense oligonucleotides on the growth of human cervical carcinoma cells in nude mice and on the expression of HIF-1αand VEGF. The correlation between HIF-1αand VEGF was studied. This will help to research the pathological mechanism of cervical cancer and may provide new method to the treatment of cervical cancer through hypoxia inducible factor 1 alpha antisense oligonucleotides blocking up the expression of HIF-1αand VEGF.Methods:Tumors were established by injection of 1×108 tumor cells named Hela into the shoulder of nude mice. The mice were classified randomly into three groups when the inoculation carcinoma grows to one centimeter and treated with saline, antisense oligonucleotide HIF-1α, sense oligonucleotide HIF-1αrespectively. Injection dose was 100μg once, which was carried out for eight times. Effects of growth suppression wereobserved through the volume and the average weight of neoplasia; the expression of HIF-la and VEGF was examined through immunohistochemical stain. The data was assayed using SPSS11.0 software.Results:1. The carcinoma cell growth curve was significantly lower after treated with as-HIF-lα. The differences of the average volume and the average weight of neoplasia were statistical significance in group C (treated with as-HIF-lα) (P<0.05).2. The expression of HIF-lαin group C was lowest in all the groups (P<0.05).3. The expression of VEGF in group C was lowest in all the groups (P<0.05).Conclusion:1. Hpoxia inducible factor 1 alpha antisense oligonucleotides have obviously inhibiting effect on inoculation carcinoma.2. The mechanism is to inhibit the expression of VEGF through inhibiting HIF-1α. As a result, the formation of tumor vessel was inhibited and the tumor apoptosis was induced.