The Investigation Of Influence Of Micro-environmental Hypoxia On Chemo-sensitivity In Human Colorectal Carcinoma

【AIM】This investigation aims at approaching the existence of micro-environmental hypoxia in human colorectal carcinoma tissues,and the correlations and molecular mechanisms with the drug resistance during chemo-therapy.【METHODS】78 tumor samples from patients diagnosed with colorectal adenocarcinoma were stained with immunohistochemical staining to observe the expression of HIF-1α,P-Gp protein,and then the correlation between HIF-1αand P-Gp was analyzed.The expression of HIF-1α,mdr1/P-Gp were detected by RT-PCR and western-bolt assays under normoxia and hypoxia circumstances in vitro.【RESULTS】The positive rate of HIF-1αin tumor tissues was 67.9%(53/78),and the positive rate of P-Gp in tumor tissues was 62.8%(49/78).Under normoxia circumstance,there were over-expressions of HIF-1αand mdr1/P-Gp in human colorectal cancer cell line.With the hypoxia time extensions,there was a time-dependent up-regulation of mdr1/P-Gp in both mRNA and protein levels,and up-regulation of HIF-1αin protein levels.【CONCLUSIONS】There is a definitely significant over-expression of HIF-1α, which means there is micro-environmental hypoxia in human colorectal carcinoma tissues.The micro-environmental hypoxia may leads to the drug resistance through HIF-1α-mediated pathways which activate the expression of mdr1/P-Gp.