关键词: 卵巢癌, 缺氧诱导因子-1&alpha, 多药耐药, B细胞淋巴瘤/白血病-2

Abstract:

Abstract:Objective
To observe the  expressions of hypoxia inducible factor-1 alpha (HIF-1α),multidrun resistance(MDR1),and B cell lymphoma/leukemia-2(Bcl-2) mRNA and protein  in human ovarian cancer DDP resistant strain SKOV3/DDP after HIF-1α silencing,and to explore the mechanism of the  resistance of  SKOV3/ DDP reversed by  HIF-1α gene silencing.
Methods The ovarian cancer cell strain SKOV3(sensitivity group) and DDP resistance strain SKOV3/DDP (resistance group)were cultured in vitro and parts of the SKOV3/DDP were transfected with HIF-1α interfere plasmid pshRNA-HIF (transfection group) or control plasmid pshRNA-Control (control group).RT-PCR method was used to detect the expression levels of  HIF-1α,MDR1 and Bcl-2 mRNA;Western blotting and immunohistochemisty methods were used to determine the expression levels of HIF-1α,P-gp (MDR1 gene encoding protein),and Bcl-2 protein in  the cells.Results The expression levels of  HIF-1α,MDR1 and Bcl-2 mRNA   in sensitivity  group and transfection group  were significantly lower than those in resistance group (P<0.05) detected by RT-PCR;the expression levels of HIF-1α,MDR1,and Bcl-2 protein in sensitivity group and transfection group were significantly lower　than those in resistance group(P<0.05) determined by Western blotting and immunohistochemistry;the expression levels of MDR1,Bcl-2 mRNA and protein  in sensitivity group and transfection group had no significant difference (P>0.05).The expressions of HIF-1  α and MDR1 and Bcl -2 were closely related（correlation coefficient of mRNA,r=0.908,P=0;r=0.916,P=0；correlation coefficient of protein,r=0.773,P=0.003；r=0.862,P=0）.Conclusion The resistance of  ovarian cancer cell SKOV3 / DDP HIF-1 α gene silencing may be related to the  down-regulation of   MDR1 and Bcl-2 expressions.

Key words: ovarian tumor, hypoxia inducible factor-1 alpha, multidrug resistance, B cell lymphoma/leukemia-2