顺铂联合衣霉素对神经母细胞瘤的抑制作用及其机制

The inhibitory effect of cisplatin combined with tunicamycin on neuroblastoma and related mechanism

目的探究顺铂(DDP)联合衣霉素(TM)对人神经母细胞瘤SH-SY5Y及SK-N-SH细胞的抑制作用及其机制。方法将人神经母细胞瘤SH-SY5Y及SK-N-SH细胞分为对照组、TM组(0.4mg/LTM处理24h)、DDP组(4mg/LDDP处理24h)和DDP+TM组(0.4mg/LTM+4mg/LDDP共处理24h)。采用CCK-8实验、平板克隆实验、划痕实验、Transwell实验分别检测各组细胞的细胞活力、增殖能力、迁移能力和侵袭能力,采用免疫印迹法检测各组细胞中JAK2-STAT3-HIF1α通路相关蛋白JAK-2、p-JAK2、STAT3、p-STAT3和HIF1α的表达水平。结果实验结果显示,DDP+TM组两种细胞的细胞活力、增殖能力、侵袭能力、第12及24小时时的迁移能力及JAK2-STAT3-HIF1α通路各蛋白表达水平均显著低于其他三组(tLSD=2.14~78.95,P<0.05)。结论DDP联合TM可通过JAK2-STAT3-HIF1α通路抑制神经母细胞瘤的增殖和迁移,该结果为神经母细胞瘤的治疗提供了新思路。

Objective To investigate the inhibitory effect of cisplatin(DDP)combined with tunicamycin(TM)on human neuroblastoma SH-SY5Y and SK-N-SH cells and related mechanism.Methods Human neuroblastoma SH-SY5Y and SK-N-SH cells were divided into control group,TM group(treated with 0.4 mg/L TM for 24 h),DDP group(treated with 4 mg/L DDP for 24 h),and DDP+TM group(treated with 0.4 mg/L TM and 4 mg/L DDP for 24 h).CCK-8 assay,plate colony formation assay,scratch assay,and Transwell assay were used to measure the viability and proliferation,migration,and invasion abilities of cells in each group,and Western blotting was used to measure the expression levels of the JAK2-STAT3-HIF1α pathway-related proteins such as JAK-2,p-JAK2,STAT3,p-STAT3,and HIF1α in each group of cells.Results Experimental results showed that compared with the other three groups,the DDP+TM group had significantly lower viability,proliferation and invasion abilities,migration ability at 12 and 24 h,and expression levels of the JAK2-STAT3-HIF1α pathway-related proteins(t LSD=2.14-78.95,P<0.05).Conclusion DDP combined with TM can inhibit the proliferation and migration of neuroblastoma via the JAK2-STAT3-HIF1α pathway,which provides new ideas for the treatment of neuroblastoma.