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. 2016 Aug;15(4):527-34.
doi: 10.1177/1533034615588197. Epub 2015 Jun 16.

"VSports在线直播" Radiosensitization of Human Colorectal Cancer Cells by MLN4924: An Inhibitor of NEDD8-Activating Enzyme

Juefeng Wan  1 , Ji Zhu  1 , Guichao Li  1 , Zhen Zhang  2
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Radiosensitization of Human Colorectal Cancer Cells by MLN4924: An Inhibitor of NEDD8-Activating Enzyme (V体育ios版)

Juefeng Wan et al. Technol Cancer Res Treat. 2016 Aug.
Free article

Abstract

Colorectal cancer is the third most frequently diagnosed cancer and the combination of radiation with capecitabine has been shown to achieve only 15% to 25% of pathologic complete response. This study aimed to investigate the effect of MLN4924, a potent small molecule inhibitor of SKP1-Cullin-F-box proteins E3 ubiquitin ligases, as a novel radiosensitizing agent in colorectal cancer cells. Indeed, we found that MLN4924 effectively sensitized colorectal cancer cells to radiation with a sensitivity-enhancement ratio of 1. 61 for HT-29 cells and 1. 35 for HCT-116 cells. Mechanistically, MLN4924 significantly enhanced radiation-induced G2/M arrest, apoptosis, and DNA damage response through accumulation of p27 VSports手机版. Knockdown of p27 via small interfering RNA partially inhibited MLN4924-induced radiosensitization, indicating a causal role played by p27. Our study suggested that MLN4924 could be further developed as a novel radiosensitizing agent against colorectal cancer. .

Keywords: MLN4924; colorectal cancer; p27; radiosensitization. V体育安卓版.

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