透明质酸结合蛋白1在人卵巢癌细胞系中表达及其与紫杉醇敏感性的关系

Relationship of chemosensitivity to paclitaxel and HABP1 expression in ovarian cancer cell lines

目的探讨透明质酸结合蛋白1在人卵巢癌细胞系SKOV3、HO-8910PM、HO-8910LM、OVCA429和OVCA420中的表达和定位及其与紫杉醇敏感性之间的关系。方法 2007年2月至2008年12月在哈尔滨医科大学附属三院研究所应用荧光定量RT-PCR技术和免疫荧光化学法结合激光共聚焦显微镜分别检测人卵巢癌细胞系SKOV3、HO-8910PM、HO-8910LM、OVCA429和OVCA420中HABP1 mRNA和蛋白的表达以及其在细胞中的定位,MTT法分析各卵巢癌细胞系对紫杉醇的敏感性。结果 HABP1 mRNA在人卵巢癌细胞系SKOV3、OVCA429和HO-8910PM中的表达水平分别是OVCA420的3.7、2.8和2.1倍(P值均<0.05),HO-8910LM和OVCA420中HABP1 mRNA的表达水平无统计学差异(P值>0.05),激光共聚焦显示5种人卵巢癌细胞系中HABP1蛋白的表达变化趋势与mRNA水平基本一致,其中SKOV3、OVCA429和HO-8910PM细胞系中HABP1蛋白在细胞核周的表达量明显高于OVCA420和HO-8910LM。MTT分析显示,SKOV3、OVCA429、OVCA420、HO-8910PM和HO-8910LM细胞对紫杉醇的中效浓度分别是:0.047μmol/L、0.221μmol/L、0.723μmol/L、0.092μmol/L和0.672μmol/L,相关分析显示HABP1 mRNA表达水平与卵巢癌细胞对紫杉醇的中效浓度之间的相关系数为-0.888,P<0.05。结论 HABP1的表达与卵巢癌细胞对紫杉醇的敏感性呈显著正相关,其机制可能是由于其在细胞中的分布位置不同所致,HABP1可作为筛选卵巢癌化疗药物的指标之一。

Objective To study the expression and localization of HABP1 in human ovarian cancer cell lines, and the correlation between HABP1 expression and chemosensitivity to paclitaxel of ovarian cancer cells. Methods Fluorescent quantitative RT-PCR were used to examine the differential expression of HABP1 mRNA at the oncobiology key laboratory of the Third Affiliated Hospital of Harbin Medical University Between Feb. 2007 and Dec. 2008. Immunofluore scence staining and confocal microscopy detected the expression and localization profiles of HABP1 protein. MTT assay was used to determine the chemosensitivity to paclitaxel of the five cell lines. Results The levels of HABP1 mRNA in SKOV3, OVCA429 and HO-8910PM were respectively 3.7,2. 8 and 2. 1 fold in comparison to that in OVCA420 （P 〈0. 05）. The level of HABP1 mRNA in HO-8910LM was not significantly distinct from that in OVCA420 （P 〉 0. 05）. The expression profiles of HABP1 protein coincided with that of HABP1 mRNA in ovarian cancer cell lines. The protein levels concen- trated in perinuclear of SKOV3, OVCA429 and HO-8910PM were higher than that of OVCA420 and HO-8910LM. The median-effect concentrations of paclitaxel to SKOV3, OVCA429, OVCA420, HO-8910PM and HO-8910LM cell lines were respectively 0. 047μmol/L, 0. 221μmol/L, 0. 723μmol/L, 0. 092μmol/L and 0. 672μmol/L. Significant correlation was found between the levels of HABP1 mRNA and the median-effect concentrations of paclitaxel （ r = - 0. 888, P 〈 0. 05）. Conclusion The expression of HABP1 was positively related to the sensitivity of paclitaxel to ovarian cancer cell lines and that may be caused by the different localization of HABP1 protein. HABP1 may be a new marker for predicting chemosensitivity to paclitaxel of ovarian cancer cells.