Notch1信号抑制对成骨肉瘤细胞化疗药物敏感性的影响
Journal of Regional Anatomy and Operative Surgery(2012)
Abstract
目的研究抑制Notch1信号对成骨肉瘤细胞化疗药物敏感性的影响及部分机制。方法将人成骨肉瘤细胞系OS-732按γ-分泌酶抑制剂(GSI)作用与否分为GSI组和对照组;脂质体法转染真核细胞表达质粒;Realtime PCR检测NICD、Hes1mRNA表达;流式细胞仪(FACS)检测Annexin V-PE/7-AAD双标的细胞凋亡;MTT法检测化疗药物对细胞的抑制率。结果 GSI组NICD和Hes1 mRNA均较对照组明显降低(P<0.01)。GSI组化疗药物导致的瘤细胞抑制率和凋亡率均明显高于对照组。过表达Hes1可减弱GSI诱导的瘤细胞化疗药物敏感性增高。结论 GSI通过抑制Notch1受体激活和下游靶基因Hes1表达促进人成骨肉瘤细胞凋亡,从而增加人成骨肉瘤细胞对化疗药物的敏感性。
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Key words
γ-secretase inhibitor,sensitivity to chemotherapy,cell apoptosis,Notch1,osteosarcoma cells
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