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Nutlin-3, an Antagonist of MDM2, Enhances the Radiosensitivity of Esophageal Squamous Cancer with Wild-Type p53
Murine double minute 2 (MDM2) negatively regu-
lates the activity of the p53 protein and plays a vital role in cell
cycle arrest, apoptosis, and senescence mediated by p53.
Nutlin-3, an antagonist of MDM2, is frequently used in anti-
cancer studies. In many human tumors, nutlin-3 stabilizes p53
status and enhances p53 expression in cells with wild-type
p53. However, the effect of nutlin-3 combined with radiother-
apy on esophageal squamous cancer (ESCC) has not been
reported. In this study, we examined whether nutlin-3 in-
creases the radiosensitivity of ESCC in vitro and in vivo.
We chose two cell lines, ECA-109 (wild-type p53) and TE-
13 (p53 mutated), for the following experiments. Cell prolif-
eration and clonogenic survival experiments showed that
nutlin-3 inhibits the cell growth and colony formation of
ECA-109 cells in a dose-dependent manner. Flow cytometry
analysis showed that the apoptosis rate of ECA-109 cells co-
treated with nutlin-3 and irradiation(IR) was significantly in-
creased compared with cells treated with irradiation or nutlin-
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