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Pevonedistat targeted therapy inhibits canine melanoma cell growth through induction of DNA re-replication and senescence

Vet Comp Oncol. 2019-10-01; 
Elizabeth A Wood, Zhanping Lu, Shuai Jia, Anna L F V Assumpção, Matthew A Van Hesteren, Mike K Huelsmeyer, David M Vail, Xuan Pan
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GenParts™ DNA Fragments … The sequences of specific primers for each gene, synthesized by GenScript (GenScript USA Inc., Piscataway, NJ, USA), were as follows … CCAGCGTGCATTTTTTCCAACTCGAG-3′. Fragments were subcloned into the pRNAT-U6.2/Lenti siRNA expression vector (Invitrogen Life … Get A Quote

摘要

MLN4924 (pevonedistat) is a potent and selective NEDD8-activating enzyme (NAE) inhibitor. The NEDD8-regulated neddylation system is responsible for the regulated degradation of intracellular proteins with important cellular functions in cancer cell growth, apoptosis, angiogenesis and metastasis. In human melanoma, inhibition of NAE results in induction of DNA re-replication, S phase cell cycle arrest, DNA damage and apoptosis. The study aimed to assess the anti-cancer effect of MLN4924 on canine malignant melanoma cell lines and patient samples and to elucidate the underlying mechanisms. Canine melanoma cell lines and primary patient samples were evaluated for cell viability after incubation with varying concen... More

关键词

DNA re-replication, MLN4924, NAE-inhibitor, canine, melanoma, senescence