缺氧条件下YC-1对人胰腺癌细胞VEGF和GPI基因的抑制效应  

Inhibitory effect of YC-1 on induction of VEGF and GPI genes in hypoxic human pancreatic cancer cells

作　　者：杜静[1] 赵秋[1] 谷华[1] 滕晓丽[1] 覃华[1] 刘南植[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院消化内科,武汉430030

出　　处：《中华肿瘤杂志》2006年第7期486-489,共4页Chinese Journal of Oncology

摘　　要：目的探讨缺氧条件下3-(5’-hydroxymethyl-2’-furyl)-1-benzylindazole(YC-1)对人胰腺癌细胞血管内皮生长因子(VEGF)和磷酸葡萄糖异构酶(GPI)基因的调控作用及其机制。方法缺氧条件下体外培养胰腺癌PC-3细胞株,免疫细胞化学染色法检测常氧和缺氧条件下缺氧诱导因子- 1α(HIF-1α)的表达。半定量RT-PCR检测YC-1对PC-3细胞VEGF、GPI、HIF-1αmRNA表达的调节作用。Western blot检测YC-1对PC-3细胞HIF-1α蛋白表达的调节作用。MTT法检测YC-1对缺氧PC-3细胞恶性增殖的影响。结果缺氧条件下,HIF-1α主要表达于PC-3细胞胞核内。随着YC-1浓度升高,VEGF和GPI mRNA表达、HIF-1α蛋白表达逐渐受抑,并呈明显的剂量依赖性;实验组HIF- 1αmRNA均呈强表达,其表达水平不随YC-1作用浓度的升高而降低。缺氧条件下,实验组细胞增殖抑制率均增高,100μmol／L YC-1组细胞增殖抑制率达73．28%±2．01％。结论缺氧状态下,YC-1抑制人胰腺癌PC-3细胞VEGF和GPI基因转录与其抑制HIF-1α蛋白的表达有关,YC-1能够抑制PC-3细胞生长和增殖。Objective To investigate the function and mechanism of 3-（5′-hydroxymethyl-2′- furyl）-1-benzylindazole （YC-1） on activity of VEGF and GPI genes in human pancreatic cancer PC-3 cells incubated under hypoxic conditions. Methods Human pancreatic cancer PC-3 cells were incubated under hypoxic culture conditions. Immunocytochemical staining was used to detect HIF-1α protein expression in hypoxic and normoxic PC-3 cells. Semi-quantitative RT-PCR was used to detect the effect of YC-1 on the expression of VEGF and GPI mRNA and HIF-1α protein in PC-3 cells. Effect of YC-1 on the expression of H/F-1α protein was examined by Western blotting. MTT assay was used to detect prohferation of hypoxic PC-3 cells. Results HIF-1α expression was mainly located in nuclei in hypoxic PC-3 cells. The mRNA synthesis of VEGF and GPI and the protein expression of HIF-1α were significantly decreased in the group treated with the highest concentration of YC-1 （100 μmol/L）. Compared to placebo, YC-1 inhibited the proliferation of hypoxic PC-3 cells greatly when it was increased to 100 μmol/L. Conclusion YC-1 inhibited the transcription of VEGF and GPI in hypoxic human pancreatic cancer PC-3 cells. It was induced by down-regulation of HIF-1α protein. YC-1 inhibites the proliferation of PC-3 cells exposed to hypoxic conditions.

关 键 词：YC-1 胰腺肿瘤 血管内皮生长因子 磷酸葡萄糖异构酶 

分 类 号：R735.9[医药卫生—肿瘤]