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Expression and significance of hypoxia-inducible factor-1 alpha and MDR1/P-glycoprotein in human colon carcinoma tissue and cells

Z. Ding,Li Yang,Xiaodong Xie,F. Xie,Feng Pan,Jianjun Li,Jian-ming He,Houjie Liang

Published 2010 in Journal of Cancer Research and Clinical Oncology

ABSTRACT

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 PaO2 cultural 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.

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