蛋白激酶CK2抑制剂对肺癌细胞系放射敏感性的影响

目的 探讨蛋白激酶CK2抑制剂对肺癌细胞系放射敏感性的影响。方法 通过蛋白印迹法检测蛋白激酶CK2α、β亚基在不同肺癌细胞系中的表达情况。平板克隆形成试验检测CK2激酶抑制剂醌茜素对肺腺癌细胞A549和大细胞肺癌细胞H460对X线的放射敏感性影响。流式细胞术检测醌茜素与X线联合作用对A549、H460细胞凋亡及周期分布影响。组间比较采用方差分析和成组t检验。结果 蛋白激酶CK2α、β亚基在对放射不敏感的A549、H1650、H460细胞中高表达, 而在放射敏感的小细胞肺癌H446细胞中低表达。使用醌茜素预处理的A549、H460细胞存活分数(SF)明显低于未处理组, 25 μmol/L的增敏比(D₀值比)分别为2.771、2.463。醌茜素可引起细胞凋亡增加, 但X线联合醌茜素与单独醌茜素作用相比未增加A549细胞和H460细胞凋亡(X线照射+醌茜素:单独醌茜素, A549细胞P= 0.487和H460细胞P=0.254), 然而X线联合醌茜素与单独X线照射或醌茜素作用相比可明显引起其G₂+M期阻滞(X线照射+醌茜素:单独X线照射, A549细胞P=0.000, H460细胞P=0.0024;X线照射+醌茜素:单独X线照射, A549细胞P=0.000, H460细胞P=0.000)。结论 通过醌茜素抑制蛋白激酶CK2活性可增加NSCLC细胞的放射敏感性。

Effect of an inhibitor of protein kinase CK2 on radiosensitivity of human lung cancer cells

Objective To evaluate the effect of an inhibitor of protein kinase CK2 on the radiosensitivity of human lung cancer cells. Methods The protein levels of CK2 α and β subunits in different lung cancer cell lines were measured by Western blot. Clonogenic assays were performed to assess the effect of a CK2 inhibitor, quinalizarin, on the radiosensitivity of lung adenocarcinoma A549 cells and large cell lung cancer H460 cells. The effects of the combination of quinalizarin and X-ray irradiation on the apoptosis and cell cycle of A549 and H460 cells were measured by flow cytometry. The differences between two groups were analyzed by analysis of variance and t-test. Results Western blot revealed that the α and β subunits of CK2 were overexpressed in non-small cell lung cancer cells (A549, H460, and H1650 cells), which were considered insensitive to X-ray irradiation, whereas a lower expression of these two subunits were found in small cell lung cancer cells (H446 cells), which were sensitive to X-ray irradiation. The clonogenic assays showed that A549 and H460 cells pre-exposed to quinalizarin had a significantly lower survival fraction compared with the control group and had a sensitization enhancement ratio greater than 1.0(D₀ were 2.771 and 2.463 respectively). The combination of quinalizarin and X-ray irradiation did not increase the apoptosis of A549 and H460 cells (X-ray+Quinalizarin vs. Quinalizarin, A549, P=0.487 and H460, P=0.254), but caused significant G₂/M arrest compared with under X-ray irradiation only (X-ray+Quinalizarin:X-ray, A549, P=0.000;H460, P=0.002 and X-ray+Quinalizarin:Quinalizarin, A549, P=0.000;H460, P=0.000). Conclusions Quinalizarin, as a CK2 inhibitor, can increase the radiosensitivity of non-small cell lung cancer cells.