溶瘤新城疫病毒抑制IL-6诱导的人胶质母细胞瘤U87MG细胞的迁移和侵袭

Oncolytic Newcastle disease virus inhibits IL-6 induced migration and invasion of human glioblastoma U87MG cells

目的:探讨溶瘤新城疫病毒(NDV)对IL-6诱导的人胶质母细胞瘤U87MG细胞增殖、迁移和侵袭的作用及其可能的机制。方法:将U87MG细胞分为对照组、IL-6组、NDV组、NDV+IL-6组,其中IL-6组与NDV+IL-6组用75 ng/mL IL-6预处理1 h,其余组用DMEM预处理1 h,后分别用DMEM、75 ng/mL IL-6、1 HU NDV、1 HU NDV+75 ng/mL IL-6处理24 h。MTT法、细胞划痕实验和Transwell侵袭实验分别检测IL-6、NDV对U87MG细胞增殖、迁移和侵袭的影响,WB法检测各组细胞JAK2、p-JAK2、STAT3、p-STAT3和MMP2蛋白的表达水平。结果:与对照组相比,IL-6组细胞迁移率显著升高(P<0.05),侵袭细胞数目显著增多(P<0.01);与IL-6组相比,NDV+IL-6组U87MG细胞增殖率显著降低(P<0.05),细胞迁移率和侵袭细胞数目均显著降低(均P<0.01)。WB实验结果显示,与对照组相比,IL-6组p-STAT3/STAT3比值显著升高(P<0.01),NDV组p-JAK2/JAK2、p-STAT3/STAT3比值显著降低(P<0.05,P<0.01),MMP-2蛋白表达量显著降低(P<0.01);与IL-6组相比,NDV+IL-6组p-STAT3/STAT3比值、MMP-2蛋白表达量均显著降低(均P<0.05)。结论:NDV能抑制IL-6对人脑胶质瘤U87MG细胞迁移和侵袭的诱导作用,其机制可能与JAK2/STAT3信号通路的参与调控有关。

Objective:To investigate the effect of oncolytic Newcastle disease virus(NDV) on the proliferation,migration and invasion of human glioblastoma U87MG cells induced by IL-6 and its possible mechanism.Methods:U87MG cells were divided into control group,IL-6 group,NDV group and NDV+IL-6 group.The cells in IL-6 group and NDV+IL-6 group were pretreated with 75 ng/mL IL-6for 1 h,and the other groups were pretreated with DMEM for 1 h;then,the four groups were treated with DMEM,75 ng/mL IL-6,1 Hu NDV,1 Hu NDV+75 ng/mL IL-6 for 24 h,respectively.MTT assay,cell scratch test and Transwell invasion test were used to detect the effects of NDV and IL-6 on the proliferation,migration and invasion of U87MG cells,respectively.The protein expression levels of JAK2,p-JAK2,STAT3,p-STAT3 and MMP2 were detected by WB method.Results:Compared with the control group,the migration rate and number of invasive cells in IL-6 group were significantly increased(P<0.05 or P<0.01).Compared with IL-6 group,the proliferation rate of U87MG cells in NDV+IL-6 group was significantly decreased(P<0.05),and the migration rate and the number of invasive cells were significantly decreased(all P<0.01).WB results showed that compared with the control group,the p-STAT3/STAT3 ratio in IL-6 group was significantly increased(P<0.01),while the p-JAK2/JAK2 ratio,p-STAT3/STAT3 ratio and MMP-2 protein in NDV group were significantly decreased(P<0.05 or P<0.01);compared with IL-6 group,the p-STAT3/STAT3 ratio and the protein expression of MMP-2 in NDV+IL-6 group were significantly decreased(all P<0.05).Conclusion:NDV can inhibit IL-6 induced migration and invasion of human glioblastoma U87MG cells,and its mechanism may be related to its regulation of JAK2/STAT3 signaling pathway.