Department of Cell Stress Biology, Roswell Park Cancer Institute, BLSC, Buffalo, NY, USA.
Cell Cycle. 2009 Nov 15;8(22):3777-81. doi: 10.4161/cc.8.22.10121. Epub 2009 Nov 23.
Cellular senescence is characterized by irreversible loss of proliferative potential and a large, flat cell morphology. Ectopic p21 and doxorubicin induced cellular senescence in HT1080 and WI-38-tert cell lines. In the same cell lines, the Mdm2 inhibitor nutlin-3a induced p53 but, unexpectedly, caused quiescence (reversible arrest) with a small cell morphology. We discuss that Mdm antagonists could be used in combination with chemotherapy to reversibly arrest normal cells, thus protecting them during chemotherapy of cancer (cyclotherapy).
细胞衰老的特征是增殖能力的不可逆丧失和细胞形态的大而扁。p21 和阿霉素异位诱导 HT1080 和 WI-38-tert 细胞系的细胞衰老。在相同的细胞系中,Mdm2 抑制剂 nutlin-3a 诱导 p53,但出乎意料的是,导致静止(可逆停滞),细胞形态小。我们讨论 Mdm 拮抗剂可与化疗联合使用,可逆地阻滞正常细胞,从而在癌症化疗(cyclotherapy)期间保护它们。