| Object: Gliomas are the most common primary malignant tumor of the central nervous system,which threating to human life and health seriously. At present, the comprehensive treatment plan which based on surgery is taken mostly in the clinical work. chemotherapy is an important treatment after surgery, but appeared in the process of drug treatment of multi-drug resistance has been a big problem in the medical community. So to study the mechanism of occurrence of drug resistance in glioma, and guide the standardization treatment is particularly important. Overexpression of P-glycoprotein(P-gp) is a important reason of multidrug resistance(MDR). Cell biology studies have found that there is hypoxia cells which is relatively insensitive to chemotherapy in solid tumor, this is the reason why chemotherapy effect is not ideal and tumor reappeared soon after treatment. Hypoxia-inducible factor-1(HIF-1) is in the center position in cell hypoxia changes, so HIF-1α,as the active subunits of HIF-1,gots a lot of attention because of the relationship with multi-drug resistance of tumor cells.Caspase family protease plays a central role in death receptor mediated apoptosis, in recent years caspase has been found playing an important role in passing sensitivity of a variety of chemotherapeutic drugs, the relationship between apoptosis and caspase-3 is the most closely, the chemotherapy drug resistance of tumor cells will increase with the derease of caspase-3 expression. The aim of our study was to the expression of P-glycoprotein(P-gp), hypoxia-inducible factor-1α(HIF-1α), caspase-3 in human glioma tissues, analyze the relationship between them and gliomas pathology level, and analyze the relationship among them. To investigate the relationship between the micro environmental hypoxia and the mechanisms of apoptosis and multidrug resistance, to further explore the drug resistance mechanism, looking for possible target molecule for the reversal of multidrug resistance, provides an important reference for the improvement of clinical chemotherapy effect and prognosis.Methods:From September. 2009 to June. 2013, we collected 62 samples of human gliomas and 6 samples of normal brain tissues from the patients, received the operation in the Affiliated Hospital of Hebei University. The study wa focused on the expression of P-pg、HIF-1α、Caspase-3 was investigated by immunohistochemistry in 62 specimens of human gliomas,further statistical analysis relationship with glioma pathology level and the relationship among the three. Results: 1. P-gp didn’t or only weakly express in normal brain tissue, the expression grades of P-pg were:the level of P-pg was 66.67%(16/24) in grade Ⅰ-Ⅱ、81.81%(18/22) in glioma grade Ⅲ、93.75%(15/16) in glioma Ⅳ. The data shows that there is statistically significant between the expression in glioma tissues of different grades(P<0.05). With the increase of level of glioma, expression of P-pg increased. 2. The positive expression of HIF-1α wasn’t observed in the normal brain tissue, and the rates of positive expression of HIF-1α were: 12.50%(1/8), 33.33%(8/24) in grade Ⅰ-Ⅱ、90.90%(20/22) in glioma grade Ⅲ、100.00%(16/16) in glioma Ⅳ. The data shows that there is statistically significant between the expression in glioma tissues of different grades(P<0.05). With the increase of level of glioma, expression of HIF-1α increased. 3. Caspase-3 didn’t express in normal brain tissue, the rates of positive expression of Caspase-3 were: 95.83%(23/24) in grade Ⅰ-Ⅱ、86.36%(19/22) in glioma grade Ⅲ、75.00%(12/16) in glioma Ⅳ. The data shows that there is statistically significant between the expression in glioma tissues of different grades(P<0.05). With the increase of level of glioma, expression of caspase-3 decreased. 4. Using Spearman rank correlated test, it can be confirmed that the expression of caspase-3 was negatively correlation with HIF-1α as well as P-gp, as the expression of HIF-1α or P-gp increasing, the expression of caspase-3 decreasing obviously. P-gp expression was siginificantly positively correlated with HIF-1α, as the expression of HIF-1α increasing, the expression of P-gp is increasing obviously. Condusion:1. The expression of P-gp、HIF-1α are increased with the increased of glioma pathology level, as well as the expression of caspase-3 decreased. P-gp、HIF-1α、caspase-3 may play an important role in the process of tumorigenesis and development of glioma,and may be an important indicator of prognosis. 2. The expression of caspase-3 was negatively correlation with HIF-1α as well as P-gp, as the expression of HIF-1α and P-gp increasing, the expression of caspase-3 decreasing obviously. P-gp expression was siginificantly positively correlated with HIF-1α,as the expression of HIF-1a increasing,the expression of P-gp is increasing obviously. HIF-1α、caspase-3 may participate in the process of glioma multidrug resistance, multidrug resistance gene expression、tissue microenvironment hypoxia and inhibition of cell apoptosis may have synergistic effect in the process of drug resistance in glioma, and provides a new idea for revealing the mechanism of multidrug resistance. Conclusion:... |
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