Dept of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
Dept of Oncology, The First Hospital of Jinlin University, Changchun, China.
Biochem Biophys Res Commun. 2014 May 2;447(2):224-30. doi: 10.1016/j.bbrc.2014.03.082. Epub 2014 Apr 4.
Antitumor antibiotic lidamycin (LDM) is widely used in the treatment of a variety of cancers. Here we demonstrated that LDM up-regulates the expression of the tumor suppressor p53 gene by repressing Oct4 transcription. We showed that low dose LDM-induced increase of p53 expression and decrease of Oct4 expression in P19 and HCT116-p53(+/+) cells. Knockdown of Oct4 expression by siRNA led to activation of p53 in both cell lines, whereas ectopical expression of Oct4 significantly inhibited p53 expression in P19 cells. LDM-induced p53 activation was blocked by ectopical expression of Oct4.
抗肿瘤抗生素榄香烯(LDM)广泛用于多种癌症的治疗。在这里,我们证明 LDM 通过抑制 Oct4 转录而上调抑癌基因 p53 的表达。我们发现低剂量 LDM 诱导 P19 和 HCT116-p53(+/+) 细胞中 p53 表达增加和 Oct4 表达减少。siRNA 敲低 Oct4 表达导致这两个细胞系中 p53 的激活,而 Oct4 的异位表达则显著抑制 P19 细胞中 p53 的表达。LDM 诱导的 p53 激活被 Oct4 的异位表达所阻断。