UNDER NORMOX1C CONDITION HYPOXIA-INDUCIBLE FACTOR-1 (HIF-1) MAY DIRECT OR INDIRECT REGULATE MULTIDRUG RESISTANCE (MDR) GENE EXPRESSION

摘要

Objectives Hypoxia inducible factor-1 (HIF-1) is a transcription factor that senses low oxygen availability and plays key roles in cancer development. MDR (multi drug resistance) proteins are generally considered to be the major obstacle in the chemotherapeutic therapy. It is our aim to find out the relation between these two factors in chemotherapy under normoxic condition. Methods Reporter plasmid system is used to test transcriptional activity of HIF-1 and western blotting to monitor protein level in cells. Quantitative real-time reverse transcription PCR is employed to survey transcription of mRNA. Results Our study shows that cancer-resistance drugs Cis and Dcx can lead cells to a higher transcriptional activity of HIF-1 under normoxia. This improvement 'was caused by neither the accumulation of HIF-1 a protein nor the enhanced transcription of HIF-1 a mRNA. Therefore we suppose that the increased transcriptional activity of HIF-1 was result from the post-translational modulation of HIF-1 a protein molecule. Furthermore, we found mRNA levels of MDR1 are improved following the increasing transcriptional activation of HIF-1 when cells were exposed to Cis and Dox under nomoxic condition. Conclusion Thus we hypothesize that HIF-1 may directly or indirectly regulate MDR1 transcription.