Shi Xinli, Liu Jingli, Ren Laifeng, Mao Nan, Tan Fang, Ding Nana, Yang Jing, Li Mingyuan
Department of Microbiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041; Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050200, China.
Department of Repairing and Servicing Technology of Medical Equipment, Bethune Medical Non-commissioned Officer Academy of PLA, Shijiazhuang, Hebei 050081, China.
BMB Rep. 2014 Apr;47(4):221-6. doi: 10.5483/bmbrep.2014.47.4.146.
Drug-resistance and imbalance of apoptotic regulation limit chemotherapy clinical application for the human hepatocellular carcinoma (HCC) treatment. The reactivation of p53 is an attractive therapeutic strategy in cancer with disrupted-p53 function. Nutlin-3, a MDM2 antagonist, has antitumor activity in various cancers. The post-translational modifications of p53 are a hot topic, but there are some controversy ideas about the function of phospho-Ser392-p53 protein in cancer cell lines in response to Nutlin-3. Therefore, we investigated the relationship between Nutlin-3 and phospho-Ser392-p53 protein expression levels in SMMC-7721 (wild-type TP53) and HuH-7 cells (mutant TP53). We demonstrated that Nutlin-3 induced apoptosis through down-regulation phospho-Ser392-p53 in two HCC cells. The result suggests that inhibition of p53 phosphorylation on Ser392 presents an alternative for HCC chemotherapy.
耐药性和凋亡调控失衡限制了化疗在人类肝细胞癌（HCC）治疗中的临床应用。p53的重新激活是一种在p53功能受损的癌症中颇具吸引力的治疗策略。Nutlin-3是一种MDM2拮抗剂，在多种癌症中具有抗肿瘤活性。p53的翻译后修饰是一个热门话题，但关于磷酸化丝氨酸392-p53蛋白在癌细胞系中对Nutlin-3反应的功能存在一些争议观点。因此，我们研究了Nutlin-3与SMMC-7721（野生型TP53）和HuH-7细胞（突变型TP53）中磷酸化丝氨酸392-p53蛋白表达水平之间的关系。我们证明，Nutlin-3通过下调两种肝癌细胞中的磷酸化丝氨酸392-p53诱导凋亡。结果表明，抑制p53丝氨酸392位点的磷酸化是肝癌化疗的一种替代方法。
