白细胞介素37对宫颈癌HeLa细胞顺铂化疗敏感性的增强作用

Enhancement of IL-37 in chemosensitivity of cervical cancer HeLa cells to cisplatin

目的:通过将白细胞介素37(IL-37)基因转染到宫颈癌HeLa细胞中,探讨IL-37对宫颈癌细胞的杀伤作用及其对宫颈癌细胞化疗敏感性的增强作用。方法:将重组pIRES2-EGFP/IL-37质粒(IL-37组)和pIRES2-EGFP质粒(NC组)分别转染到HeLa细胞。Q-PCR和Western blotting法检测IL-37基因和蛋白表达水平;CCK8法检测NC组、IL-37组、顺铂(DDP)组及IL-37+DDP组细胞活性,计算细胞抑制率;RT-PCR法检测信号转导和转录激活因子3(STAT3)及细胞周期蛋白D1(Cyclin D1)mRNA表达水平。结果:与NC组比较,IL-37组IL-37mRNA和蛋白表达水平明显升高(P<0.01)。给药后24~72h,5~15mg·L-1 DDP组HeLa细胞活性受到明显抑制(P<0.01);与DDP组比较,IL-37+DDP组HeLa细胞抑制率在处理后48h内明显升高(P<0.05);与IL-37组比较,IL-37+DDP组HeLa细胞抑制率在处理后96h内均有升高(P<0.05)。与NC组比较,IL-37组STAT3和Cyclin D1mRNA表达水平明显下降(P<0.01)。结论:IL-37高表达可抑制宫颈癌细胞的增殖,并能增强DDP对宫颈癌细胞的放疗效果,这种效应的发挥可能与IL-37使STAT3和Cyclin D1表达下调有关。

Objective：To transfer the interleukin 37（IL-37）gene to cervical cancer Hela cells,and to explore the killing effect of IL-37 on the HeLa cells and its enhancement in the chemotherapy sensitivity of HeLa cells.Methods：The pIRES2-EGFP（NC group）and pIRES2-EGFP/IL-37（IL-37 group）plasmids were transfected into the HeLa cells.Q-PCR and Western blotting methods were used to detect the expression levels of IL-37 mRNA and protein.The activities of HeLa cells in NC group,IL-37 group,DDP group and IL-37＋DDP group were detected by CCK8 method,and the inhibitory rates of cells were calculated.The gene expressions of signal transducer and activator of transcription 3（STAT3）and Cyclin D1 were detected by RT-PCR method.Results：Compared with NC group,the expression levels of IL-37 mRNA and protein in IL-37 group were significantly increased（P〈0.01）.The activities of HeLa cells in DDP（5-15mg·L^-1）groups were inhibited after administration for 24-72h（P〈0.01）;the inhibitory rates in IL-37＋ DDP group were higher than those in DDP group within 48 h after administration（P〈0.05）.Compared with IL-37 group,the inhibitory rates in IL-37＋DDP group was increased with 96 hafter administration（P〈0.05）.Compared with NC group,the expression levels of STAT3 and Cyclin D1 mRNA in IL-37 group were significantly decreased（P〈0.01）.Conclusion：The over-expression of IL-37 can inhibit the proliferation of cervical cancer cells and enhance the effect of DDP on the chemotherapy of cervical cancer cells which may be related to the down-regulation of the expressions of STAT3 and Cyclin D1 by IL-37.