Expression and significance of hypoxia-inducible factor-1 alpha and MDR1/P-glycoprotein in human colon carcinoma tissue and cells.
Expression and significance of hypoxia-inducible factor-1 alpha and MDR1/P-glycoprotein in human colon carcinoma tissue and cells.
复制标题
缺氧诱导因子1α和MDR1/P-糖蛋白在人结肠癌组织和细胞中的表达及意义
DOI：
10.1007/s00432-010-0828-5
复制
发表时间：
2010-11
影响因子：
3.6
通讯作者：
Liang, Houjie
中科院分区：
文献类型：
--
作者：
Ding, Zhenyu;Yang, Li;Xie, Xiaodong;Xie, Fangwei;Pan, Feng;Li, Jianjun;He, Jianming;Liang, Houjie
目的肿瘤缺氧通常与化学抗性和放射抗性相关。然而，异二聚体缺氧诱导因子1（HIF-1）与多药耐药（MDR1）基因/转运蛋白P-糖蛋白（P-gp）之间的相关性尚未得到明确研究。本研究旨在检测HIF-1α和MDR1/P-gp在人结肠癌组织和细胞系（HCT-116、HT-29、LoVo和SW480）中的表达水平，并确定HIF-1α是否在MDR1/P-gp的肿瘤多药耐药中发挥重要作用。方法通过检测HIF-1α和P-gp蛋白在人结肠癌组织和细胞系中的表达和分布。使用链霉亲和素/过氧化物酶（SP）和双标记免疫荧光方法进行免疫组织化学和免疫细胞化学。分别在常氧和低氧条件下采用RT-PCR分析细胞系中HIF-1α和MDR1 mRNA的表达水平。结果免疫组化方法显示HIF-1α和P-gp表达与性别、年龄、部位和分化程度无关（P>0.05）。但HIF-1α和P-gp在不同Dukes分期的表达以及是否参与淋巴侵袭方面存在显着性差异（P<0.05）。相关分析显示HIF-1α蛋白表达量与P-gp表达量显着相关（P<0.01）。双标免疫荧光显示人结肠癌组织中确实存在HIF-1α和P-gp的共表达。常氧和缺氧条件下四种人结肠癌细胞系中均检测到HIF-1α和MDR1 mRNA的表达。缺氧条件下同类型细胞中 HIF-1α 和 MDR1 mRNA 表达水平的光密度值分别显着高于常氧条件下（P < 0.01）。然而，在相同PaO2培养条件下，这些细胞系中HIF-1α或MDR1 mRNA表达没有发现显着差异（P>0.05）。免疫细胞化学结果与mRNA表达分析相符。结论提示缺氧诱导结肠癌中HIF-1α和MDR1/P-gp的表达，且HIF-1α表达可能与MDR1（P-gp）基因相关，交互参与肿瘤多药耐药的发生。
PurposeHypoxia in tumors is generally associated with chemoresistance and radioresistance. However, the correlation between the heterodimeric hypoxia-inducible factor-1 (HIF-1) and the multidrug resistance (MDR1) gene/transporter P-glycoprotein (P-gp) has not been clearly investigated. This study aims at examining the expression levels of HIF-1α and MDR1/P-gp in human colon carcinoma tissues and cell lines (HCT-116, HT-29, LoVo, and SW480) and ascertaining whether HIF-1α plays an important role in tumor multidrug resistance with MDR1/P-gp.MethodsThe expression and distribution of HIF-1α and P-gp proteins were detected in human colon carcinoma tissues and cell lines by immunohistochemistry and immunocytochemistry using streptavidin/peroxidase (SP) and double-label immunofluorescence methods. HIF-1α and MDR1 mRNA expression levels in cell lines were analyzed using RT-PCR under normoxic and hypoxic conditions, respectively.ResultsThe immunohistochemical method shows that HIF-1α and P-gp expression were not correlated with gender, age, location, and differentiation degree (P> 0.05). However, the expression of HIF-1α and P-gp at different Dukes’ stages and whether involved in lymphatic invasion shows a significant difference (P< 0.05). Correlation analysis displays that HIF-1α protein expression was correlated significantly with P-gp expression (P< 0.01). Double-label immunofluorescence demonstrates that coexpression of HIF-1α and P-gp does exist in human colon carcinoma tissues. The mRNA expression of HIF-1α and MDR1 was detected in the four human colon carcinoma cell lines under both normoxia and hypoxia. Optical density values representing mRNA expression levels of HIF-1α and MDR1 were found to be significantly higher in the same type cells under hypoxic conditions than that under normoxic conditions, respectively (P< 0.01). However, no significant differences of HIF-1α or MDR1 mRNA expression were found among these cell lines, which exposed under the same PaO2cultural conditions (P> 0.05). And the immunocytochemistry results were corresponding with the analysis of mRNA expression.ConclusionsThese results suggest that hypoxia induce the expression of HIF-1α and MDR1/P-gp in colon carcinoma and HIF-1α expression may be associated with the gene MDR1 (P-gp) and interactively involved in the occurrence of tumor multidrug resistance.
登录
查看更多内容
DOI：
10.1016/s0360-3016(02)02848-1
发表时间：
2002-08-01
影响因子：
7
作者：
Koukourakis, MI;Giatromanolaki, A;Harris, AL
通讯作者：
Harris, AL
影响因子：
64.8
作者：
Maxwell, PH;Wiesener, MS;Ratcliffe, PJ
通讯作者：
Ratcliffe, PJ
影响因子：
64.8
作者：
RONINSON, IB;ABELSON, HT;VARSHAVSKY, A
通讯作者：
VARSHAVSKY, A
DOI：
10.1093/jnci/93.24.1879
发表时间：
2001-12-19
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Matthews, NE;Adams, MA;Graham, CH
通讯作者：
Graham, CH
DOI：
10.1006/bbrc.2001.5927
发表时间：
2001-11-23
影响因子：
3.1
作者：
Oikawa, M;Abe, M;Sato, Y
通讯作者：
Sato, Y