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- Title
Nutlin-3, an Antagonist of MDM2, Enhances the Radiosensitivity of Esophageal Squamous Cancer with Wild-Type p53.
- Authors
He, Tianli; Guo, Jiayou; Song, Hongmei; Zhu, Hongcheng; Di, Xiaoke; Min, Hua; Wang, Yuandong; Chen, Guangzong; Dai, Wangshu; Ma, Jianhua; Sun, Xinchen; Ma, Jianxin
- Abstract
Murine double minute 2 (MDM2) negatively regulates 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 radiotherapy on esophageal squamous cancer (ESCC) has not been reported. In this study, we examined whether nutlin-3 increases 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 proliferation 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 increased compared with cells treated with irradiation or nutlin-3 alone. Western blotting detected the expression of apoptosis-associated proteins in ECA-109 cells in response to nutlin-3 and irradiation. These effects were not evident in TE-13 cells. Xenograft mouse models indicated that nutlin-3 suppresses tumor growth and promotes radiosensitivity in the ESCC cell line ECA-109 in vivo. We have demonstrated that co-treatment of nutlin-3 with irradiation can significantly inhibit the growth and improve the radiosensitivity of ESCC cells with wild-type p53. The study suggests that nutlin-3 may be a potent therapeutic agent in conjunction with radiotherapy in ESCC.
- Subjects
TREATMENT of esophageal cancer; P53 protein; CELL cycle; APOPTOSIS; CELL proliferation; RADIOTHERAPY
- Publication
Pathology & Oncology Research, 2018, Vol 24, Issue 1, p75
- ISSN
1219-4956
- Publication type
Article
- DOI
10.1007/s12253-017-0215-5