Superinduction of wild-type p53 protein after 2-methoxyestradiol treatment of Ad5p53-transduced cells induces tumor cell apoptosis
Superinduction of wild-type p53 protein after 2-methoxyestradiol treatment of Ad5p53-transduced cells induces tumor cell apoptosis
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Ad5p53转导细胞经2-甲氧基雌二醇处理后野生型p53蛋白的超诱导诱导肿瘤细胞凋亡
作者：
T. Mukhopadhyay;J. Roth
由于2-甲氧基乙烯基吡咯烷酮（2-MeOE 2）诱导和稳定野生型p53蛋白（野生型p53）在人肺癌细胞系转录后，我们试图研究其对Ad 5 p53转导的肺癌细胞系在低感染复数（1 MOI）的影响。用2-MeOE 2处理这些细胞会导致wt p53蛋白表达的超诱导，随后出现细胞凋亡，如末端脱氧核苷酸转移酶（TdT）染色所示，以及wt p53表达的上调，如蛋白质印迹分析所示。当以1 MOI单独用Ad 5 p53转导时，细胞系快速生长。此外，腺病毒载体介导的p53基因转移，然后2-MeOE 2治疗引起80%的细胞系的生长抑制，无论其p53的状态。因此，p53超诱导和细胞凋亡后，2-MeOE 2处理的Ad 5 p53转导的细胞似乎是一个独特的策略，具有显着的意义，为癌症基因治疗。
Because 2-methoxyestradiol (2-MeOE2) induces and stabilizes wild-type p53 protein (wt p53) in human lung cancer cell lines posttranscriptionally, we sought to study its effects on Ad5p53-transduced lung cancer cell lines at a low multiplicity of infection (1 MOI). Treating these cells with 2-MeOE2 resulted in superinduction of wt p53 protein expression followed by apoptosis, as shown by terminal deoxynucleotidyl transferase (TdT) staining, and upregulation of wt p53 expression, as shown by Western blot analysis. When transduced with Ad5p53 alone at 1 MOI, the cell lines grew rapidly. Moreover, adenoviral-vector-mediated p53 gene transfer followed by 2-MeOE2 treatment caused 80% growth inhibition in the cell lines regardless of their p53 status. Thus, p53 superinduction and apoptosis after 2-MeOE2 treatment in Ad5p53-transduced cells appears to be a unique strategy with significant implications for cancer gene therapy.