Study Of Antisense Hypoxia Inducible Factor-1α Revering The Phenotype Of Multidurg Resistance In Human Breast Cancer

Background: The multidurg resistance (MDR) of the tumor is the most important obstacle in clinical therapy. And it is also the main reason that leads to the clinical chemotherapy failure and results in relapse or distant metastasis of breast cancer. Primary breast cancer is much sensitive to chemotherapy and most of them can alleviate by using difference structural cytoxious drugs, but most of them come into being multidurg resistance soon which lead to high relapse rate and poor prognosis of breast cancer. The mechanism of MDR is much complex. One of the mechanisms underlying MDR has been assigned to enhanced removal of drugs due to over-expression of mdr1 gene which encode efflux transporter protein, such as P-glycoprotein (P-gp). Overexpression of P-gp has been shown to correlate with multidrug resistance in numerous multidrug resistant cell lines. At present, it is not fully understood how P-gp over-expression was mediated in cancer, so more attentions were put on the mechanisms of drug resistance and reversal stategies. Besides the mdrl gene and its protein P-gp, the relationship between the changes of cell microenvironment and MDR becomes a new hotspot. The most important change of cell microenvironment was the ischemia and hypoxia. Since hypoxia-inducible factor-1(HIF-1) plays an important role in cell microenvironment changes, it is very interesting to investigate the relationship between MDR and HIF-1.The microenvironment of rapidly growing tumors is associated with increased energy demand and diminished vascular supply, resulting in focal areas of prominent hypoxia. Hypoxia is an acknowledged feature of most solid tumors .The ability of tumors to adapt to a hypoxic microenvironment was increasingly recognized as an...