Tags

Type your tag names separated by a space and hit enter

MDM2 antagonist can inhibit tumor growth in hepatocellular carcinoma with different types of p53 in vitro.
J Gastroenterol Hepatol. 2011 Feb; 26(2):371-7.JG

Abstract

BACKGROUND AND AIMS

Nutlin-3, a selective small-molecule inhibitor of the p53-MDM2 interaction, has been shown to have antitumor activities in various tumors with wild-type p53. However, its effect on hepatocellular carcinoma (HCC) with different types of p53 remains unclear. This study is designed to determine nutlin-3's antitumor efficacy and underlying mechanisms of action in human HCC cells.

METHODS

Cell viability assay, cell cycle analysis, apoptosis assay, western blot, co- immunoprecipitation and siRNA experiments were analyzed in three human HCC cells. Anti-tumoral effects of nutlin-3 targeting the p53 and p73 pathways were evaluated in HCC cell lines.

RESULTS

Nutlin-3 exerted the greatest anti-tumoral effect to three human HCC cells with wild-type p53, mutant p53 and p53-null. Nutlin-3 not only upregulated p53 in HepG2 cells, but also p73 in Huh7 and Hep3B cells, and disrupted p53-MDM2 and p73-MDM2 complexes in HCC cells. The compound inhibited cell proliferation, induced G0/G1 phase arrest, decreased the levels of CyclinD1, CyclinE, CDK2, CDK4, PCNA and E2F-1, and increased the levels of p21 and p27. It also induced apoptosis, increased the Bax/Bcl-2 ratio, then activated caspase-9 and caspase-3.

CONCLUSIONS

Nutlin-3 has significant anticancer effects against human HCC cells, regardless of p53 status, indicating that it is a promising therapy for human hepatocellular carcinoma.

Authors+Show Affiliations

Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21261729

Citation

Wang, Jiabei, et al. "MDM2 Antagonist Can Inhibit Tumor Growth in Hepatocellular Carcinoma With Different Types of P53 in Vitro." Journal of Gastroenterology and Hepatology, vol. 26, no. 2, 2011, pp. 371-7.
Wang J, Zheng T, Chen X, et al. MDM2 antagonist can inhibit tumor growth in hepatocellular carcinoma with different types of p53 in vitro. J Gastroenterol Hepatol. 2011;26(2):371-7.
Wang, J., Zheng, T., Chen, X., Song, X., Meng, X., Bhatta, N., Pan, S., Jiang, H., & Liu, L. (2011). MDM2 antagonist can inhibit tumor growth in hepatocellular carcinoma with different types of p53 in vitro. Journal of Gastroenterology and Hepatology, 26(2), 371-7. https://doi.org/10.1111/j.1440-1746.2010.06440.x
Wang J, et al. MDM2 Antagonist Can Inhibit Tumor Growth in Hepatocellular Carcinoma With Different Types of P53 in Vitro. J Gastroenterol Hepatol. 2011;26(2):371-7. PubMed PMID: 21261729.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MDM2 antagonist can inhibit tumor growth in hepatocellular carcinoma with different types of p53 in vitro. AU - Wang,Jiabei, AU - Zheng,Tongsen, AU - Chen,Xi, AU - Song,Xuan, AU - Meng,Xianzhi, AU - Bhatta,Nishant, AU - Pan,Shangha, AU - Jiang,Hongchi, AU - Liu,Lianxin, PY - 2011/1/26/entrez PY - 2011/1/26/pubmed PY - 2011/4/9/medline SP - 371 EP - 7 JF - Journal of gastroenterology and hepatology JO - J. Gastroenterol. Hepatol. VL - 26 IS - 2 N2 - BACKGROUND AND AIMS: Nutlin-3, a selective small-molecule inhibitor of the p53-MDM2 interaction, has been shown to have antitumor activities in various tumors with wild-type p53. However, its effect on hepatocellular carcinoma (HCC) with different types of p53 remains unclear. This study is designed to determine nutlin-3's antitumor efficacy and underlying mechanisms of action in human HCC cells. METHODS: Cell viability assay, cell cycle analysis, apoptosis assay, western blot, co- immunoprecipitation and siRNA experiments were analyzed in three human HCC cells. Anti-tumoral effects of nutlin-3 targeting the p53 and p73 pathways were evaluated in HCC cell lines. RESULTS: Nutlin-3 exerted the greatest anti-tumoral effect to three human HCC cells with wild-type p53, mutant p53 and p53-null. Nutlin-3 not only upregulated p53 in HepG2 cells, but also p73 in Huh7 and Hep3B cells, and disrupted p53-MDM2 and p73-MDM2 complexes in HCC cells. The compound inhibited cell proliferation, induced G0/G1 phase arrest, decreased the levels of CyclinD1, CyclinE, CDK2, CDK4, PCNA and E2F-1, and increased the levels of p21 and p27. It also induced apoptosis, increased the Bax/Bcl-2 ratio, then activated caspase-9 and caspase-3. CONCLUSIONS: Nutlin-3 has significant anticancer effects against human HCC cells, regardless of p53 status, indicating that it is a promising therapy for human hepatocellular carcinoma. SN - 1440-1746 UR - https://www.unboundmedicine.com/medline/citation/21261729/MDM2_antagonist_can_inhibit_tumor_growth_in_hepatocellular_carcinoma_with_different_types_of_p53_in_vitro_ L2 - https://doi.org/10.1111/j.1440-1746.2010.06440.x DB - PRIME DP - Unbound Medicine ER -