顺铂与XAV939联合应用对人肺癌细胞A549增殖、迁移能力的影响及机制

Effects of cisplatin combined with XAV939 on proliferation,migration and transcription factor expression in WNT pathway of human lung cancer A549 cells

目的观察顺铂联合端锚聚合酶抑制剂XAV939对人肺癌细胞增殖和迁移能力的影响,并探讨其机制。方法将体外培养的人肺癌A549细胞分为空白对照组、顺铂组、XAV939组、顺铂+XAV939组,分别用1μmol/L Na Cl、0.002 g/L顺铂、1μmol/L XAV939、0.002 g/L顺铂+1μmol/L XAV939培养。用MTT法观察各组细胞增殖情况并计算细胞增殖抑制率;用细胞划痕实验和Transwell小室实验观察各组细胞迁移能力;用Western blotting法检测各组细胞中的WNT通路转录因子端锚聚合酶、β-连接素蛋白。结果与对照组相比,顺铂组、XAV939组、顺铂+XAV939组细胞增殖抑制率高(P均<0.05),细胞迁移距离短(P均<0.05),穿膜细胞数少(P均<0.05),细胞中端锚聚合酶、β-连接素蛋白相对表达量低(P均<0.05);与顺铂组和XAV939组相比,顺铂+XAV939组细胞增殖抑制率高(P均<0.05),细胞迁移距离短(P均<0.05),穿膜细胞数少(P均<0.05),细胞中端锚聚合酶、β-连接素蛋白相对表达量低(P均<0.05)。结论顺铂联合XAV939可以抑制人肺癌A549的增殖和迁移,且效果强于单用XAV939或顺铂。这可能与二者抑制WNT通路转录因子端锚聚合酶、β-连接素蛋白表达有关。

Objective To observe the effects of cisplatin combined with tankyrase small molecule inhibitor XAV939 on the proliferation and migration of human lung cancer A549 cells and to investigate the mechanism.Methods The hu-man lung cancer A549 cells were divided into the blank control group （treated with 1 μmol/L NaCl）,cisplatin group （treated with 0.002 g/L）,XAV939 group （treated with 1 μmol/L）,and cisplatin＋XAV939 group （treated with 0.002 g/L cisplatin＋1 μmol/L XAV939）.The cell proliferation and proliferation inhibitory rates in each group were assessed by MTT assay.The cell migration ability was detected by Scratch test and Transwell chamber assay.Then,the protein expres-sion of tankyrase andβ-catenin was detected by Western blotting,respectively.Results Compared with the control group, the proliferation inhibitory rates of cells was higher,the cell migration distance was shorter,the number of transmembrane cells was less,and the protein expression ofβ-catenin and tankyrase was lower in the cisplatin group,XAV939 group,and cisplatin＋XAV939 group （all P〈0.05）.Compared with the cisplatin and XAV939 group,the proliferation inhibitory rate of the cisplatin ＋XAV939 group was higher,the cell migration distance was shorter,the number of transmembrane cells was less,and the protein expression ofβ-catenin and tankyrase was lower （all P〈0.05 ）.Conclusions Cisplatin com-bined with XAV939 may inhibit the proliferation and migration abilities of A549 cells and the combined effect is more pow-erful that of XAV939 or cisplatin alone.This effect may be correlated with the inhibition of β-catenin expression and tankyrase expression.