CXCR4抑制剂AMD3100对人卵巢癌OVCAR3细胞凋亡的影响

Effect of CXCR4 inhibitor AMD3100 on apoptosis of human ovarian cancer cell line OVCAR3

目的探讨CXCR4抑制剂AMD3100对卵巢癌细胞株OVCAR3凋亡水平及其相关蛋白表达水平的影响。方法采用免疫组织化学法检测人体卵巢癌恶性组标本中趋化因子受体4(CXCR4)、B淋巴细胞瘤/白血病-2基因(Bcl-2)、Bax、半胱氨酸蛋白酶3(caspase-3)的表达,分析其与临床病理特征的关系。不同浓度AMD3100处理OVCAR3细胞后,利用流式细胞术检测细胞凋亡情况;Western blot检测CXCR4、Bcl-2、Bax及caspase-3的表达情况。结果人体卵巢癌组织(恶性组)标本中CXCR4、Bcl-2较良性对照组表达升高,Bax较良性对照组表达降低(均P<0.05),caspase-3在两组中表达差异无统计学意义(P>0.05),恶性组中CXCR4与Bcl-2的表达呈正相关,与caspase-3呈负相关(r=0.480,-0.475,均P<0.05),Bax、Bcl-2两者表达无相关性(P>0.05);不同浓度AMD3100作用OVCAR3细胞后,Bax、caspase-3的表达增加,CXCR4及Bcl-2的表达降低,细胞的凋亡率增加,与空白对照组相比差异均有统计学意义(P<0.05)。结论 AMD3100抑制卵巢癌细胞株OVCAR3中CXCR4的表达,并能促进卵巢癌细胞的凋亡,其机制可能是通过阻断CXCR4后抑制凋亡相关蛋白Bcl-2的表达,同时促进Bax、caspase-3表达实现的。

Objective To investigate the effect of CXCR4 inhibitor AMD3100 on the level of apoptosis and the expression of related protein of ovarian cancer cell line OVCAR3.Methods Immunohistochemical method was used to detect the expression and correlation of CXCR4,Bcl-2,Bax and caspase-3 in human ovarian cancer tissues,and the relationship between the four indicators above and clinicopathological features was analyzed.After treatment of OVCAR3 cells with different concentrations of AMD3100,apoptosis was detected by flow cytometry.The expression of CXCR4,Bcl-2,Bax and caspase-3 were detected by Western blot.Results CXCR4 and Bcl-2 expression in human ovarian carcinoma specimens were higher than benign group,and Bax and caspase-3 were lower,CXCR4 expression was positively related to Bcl-2,and negatively related to caspase-3(r=0.480,-0.475,P<0.05)and there′s no relationship between Bax and Bcl-2.Different concentrations of AMD3100 act on OVCAR3,the expression of Bax,caspase-3 and cell apoptosis rate increased,the expression of Bcl-2 decreased,the differences were statistically significant when compared with the control group(P<0.05).Conclusion AMD3100 inhibited the expression of CXCR4 in ovarian cancer cell line OVCAR3,and promoted the apoptosis of ovarian cancer cells.The mechanism may be the inhibition of Bcl-2 expression by blocking CXCR4 and the promotion of Bax and caspase-3 expression.