Nutlin-3 downregulates p53 phosphorylation on serine392 and induces apoptosis in hepatocellular carcinoma cells
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Drug-resistance and imbalance of apoptotic regulation limitchemotherapy clinical application for the human hepatocellularcarcinoma (HCC) treatment. The reactivation of p53 isan attractive therapeutic strategy in cancer with disrupted-p53function. Nutlin-3, a MDM2 antagonist, has antitumor activityin various cancers. The post-translational modifications of p53are a hot topic, but there are some controversy ideas about thefunction of phospho-Ser392-p53 protein in cancer cell lines inresponse to Nutlin-3. Therefore, we investigated the relationshipbetween Nutlin-3 and phospho-Ser392-p53 proteinexpression levels in SMMC-7721 (wild-type TP53) and HuH-7cells (mutant TP53). We demonstrated that Nutlin-3 inducedapoptosis through down-regulation phospho-Ser392-p53 in twoHCC cells. The result suggests that inhibition of p53phosphorylation on Ser392 presents an alternative for HCC chemotherapy.
Abstract
Drug-resistance and imbalance of apoptotic regulation limitchemotherapy clinical application for the human hepatocellularcarcinoma (HCC) treatment. The reactivation of p53 isan attractive therapeutic strategy in cancer with disrupted-p53function. Nutlin-3, a MDM2 antagonist, has antitumor activityin various cancers. The post-translational modifications of p53are a hot topic, but there are some controversy ideas about thefunction of phospho-Ser392-p53 protein in cancer cell lines inresponse to Nutlin-3. Therefore, we investigated the relationshipbetween Nutlin-3 and phospho-Ser392-p53 proteinexpression levels in SMMC-7721 (wild-type TP53) and HuH-7cells (mutant TP53). We demonstrated that Nutlin-3 inducedapoptosis through down-regulation phospho-Ser392-p53 in twoHCC cells. The result suggests that inhibition of p53phosphorylation on Ser392 presents an alternative for HCC chemotherapy.
참고문헌 (34)
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