转录因子SOX2抑制肺癌细胞系顺铂药物敏感性的作用研究

Transcription factor SOX2 inhibit the sensitivity of cisplatin in the lung cancer cell line

目的研究Wnt/β-catenin信号与SOX2相互作用对肺癌细胞系顺铂药物敏感性的影响。方法分别以顺铂药物敏感和耐药的细胞系A549和A549/DDP为模型,转染SOX2过表达或sh SOX2质粒,采用免疫印迹法对Wnt/β-catenin信号中相关蛋白表达情况进行检测分析,运用流式细胞仪对SOX2抑制顺铂诱导的肺癌细胞凋亡进行观察。结果 SOX2过表达组中,Wnt/β-catenin信号通路的关键蛋白active-β-catenin、靶基因Cyclin D1的表达均下降,但GSK-3的表达量明显增高,而sh SOX2处理组中,ABC、Cyclin D1的表达均升高;过表达SOX2可以极显著性地抑制顺铂诱导的凋亡,反之,sh SOX2瞬时表达极显著地增加顺铂诱导的凋亡。结论 SOX2可抑制肺癌细胞中Wnt/β-catenin信号的活性,在肺癌顺铂药物耐药性中发挥重要的作用,可能作为肺癌耐药性治疗的一个新靶标。

Objective To explore the interaction of Wnt/- catenin signal pathway and the transcription factor SOX2 to the sen- sitive of cisplatin in the lung cancer cells. Methods A549 cells ware used as cisplatin sensitive model and A549/DDP cells as cisplatin resistant model. Over - expression SOX2 and shSOX2 plasmid were transfected respectively. The key proteins of Wnt/β - catenin signa- ling pathway were measured by western - blot; the apoptosis rate of lung cancer cell induced by cisplatin was detected by the flow cytom- etry. Results Compare to the control group, the expression rates of active - β - catenin and the target gene Cyclin D1 were decreased in the SOX2 group; while,the expression of ABC and Cyclin D1 were increased in the shSOX2 group. Compare to control group,over -ex- pression of SOX2 group significantly suppressed the apoptosis induced by cisplatin, instantaneously, shSOX2 significantly increased the apoptosis induced by cisplatin. Conclusion This results suggest that SOX2 may inhihit the activity of Wnt/β - catenin signal in the lung cancer cells. SOX2 may be an important regulator in development of chemoresistance,which may imply that SOX2 may be a novel thera- peutic target for treatment chemoresistant lung cancer.