低氧环境下西尼地平抑制HIF-1α下调宫颈癌HeLa细胞VEGF表达的研究  

Cilnidipine inhibits VEGF via the downregulation of HIF-1α under hypoxic conditions in HeLa cells

作　　者：袁志平[1] 牟华平 王秋[1] 王立帅[1] 陈洁[1] 张川利[1] 周光远[1] 陈家莲[1] 

机构地区：[1]宜宾市第二人民医院,四川宜宾644000

出　　处：《四川医学》2013年第11期1639-1641,共3页Sichuan Medical Journal

基　　金：宜宾市重点科技计划项目(编号:2011SF009)

摘　　要：目的探讨西尼地平能否在低氧环境下,通过抑制HIF-1α下调宫颈癌HeLa细胞VEGF的表达。方法将HeLa细胞分为常氧组(Normoxia组)、低氧环境组(Hypoxia组)、低氧环境+3μM西尼地平组(Hypoxia+3μM Cilnidipine组)和低氧环境+30μM西尼地平组(Hypoxia+30μM Cilnidipine组)。在低氧环境(1%O2、5%CO2和94%N2)下,对Hypoxia+3μM Cilnidipine组和Hypoxia+30μM Cilnidipine组细胞使用西尼地平(3μM和30μM)干预,在干预后不同时间点(0、24、48和72 h)使用MTT法对HeLa细胞活性进行测定;在干预72h后,使用RT-PCR法对细胞表达的VEGF和HIF-1αmRNA进行测定,使用Western blot法对细胞表达的VEGF和HIF-1α蛋白进行测定。结果在低氧环境下,西尼地平干预后,HeLa细胞的细胞活性呈时间和剂量依赖性降低(P均<0.05);在干预72 h后,细胞VEGF和HIF-1αmRNA和蛋白的表达水平较未干预细胞降低并呈剂量依赖性(P均<0.05)。结论在低氧环境下,西尼地平可能是通过抑制HIF-1α的表达下调HeLa细胞VEGF的表达,导致肿瘤的增殖能力降低。Objective To investigate whether cilnidipine could suppress VEGF through the downregulation of HIF-1α un- der hypoxic conditions in HeLa cells. Methods . HeLa cells were divided into 4 group, Normoxia group, Hypoxia group, Hypoxi-1α ＋ 30μM Cilnidipine group and Hypoxia ＋ 30μM Cilnidipine group. MTT assay was used to measure cell viability at specified time points （0, 24, 48 and 72h） after cilnidipine intervention. RT-PCR and western blotting were performed to analyze the mRNA and protein expression of VEGF and HIF-1αat 72h after cilnidipine intervention. Results The proliferation of HeLa cells under hy- poxie conditions was inhibited by cilnidipine in a time and dosage dependent manner. Our results showed that hypoxia led to the upregulation of VEGF and HIF-1α both at the mRNA and protein levels. Meanwhile, the hypoxia-induced overexpression of VEGF and HIF-1α was dosage dependently suppressed by cilnidipine. Conclusion Cilnidipine suppresses VEGF possibly via the down- regulation of HIF-1α under hypoxic conditions in HeLa cells.

关 键 词：西尼地平 HELA细胞 血管生成因子 低氧诱导因子-1Α 

分 类 号：R737.33[医药卫生—肿瘤]