Radiotherapy induces cell cycle arrest and cell apoptosis in nasopharyngeal carcinoma via the ATM and Smad pathways.

Abstract

Nasopharyngeal carcinoma (NPC) is a common malignant neoplasm of the head and neck which is harmful to human's health. Radiotherapy is commonly used in the treatment of NPC and it induces immediate cell cycle arrest and cell apoptosis. However, the mechanism remains unknown. Evidences suggested the activation of Ataxia telangiectasia mutated (ATM) pathway and Smad pathway are 2 of the important crucial mediators in the function of radiotherapy. In this study, we performed in vitro assays with human nasopharyngeal carcinoma CNE-2 cells and in vivo assays with nude mice to investigate the role of the ATM and Smad pathways in the treatment of nasopharyngeal carcinoma with radiotherapy. The results suggested that radiation induced activation of ATM pathway by inducing expression of p-ATM, p-CHK1, p-CHK2, p15 and inhibiting expression of p-Smad3. In addition, Caspase3 expression was increased while CDC25A was decreased, leading to cell cycle arrest and cell apoptosis. On the other hand, activation of Smad3 can inhibited the ATM pathway and attenuated the efficacy of radiation. In summary, we suggest that both ATM and Smad pathways contribute to the cell cycle arrest and cell apoptosis during nasopharyngeal carcinoma cells treated with radiation.

• Authors: Ming-Yi Li, Jin-Quan Liu, Dong-Ping Chen, Zhou-Yu Li, Bin Qi, Lu He, Yi Yu, Wen-Jin Yin, Meng-Yao Wang, Ling Lin
• Journal: Cancer biology & therapy (Cancer Biol Ther) Vol. 18 Issue 9 Pg. 681-693 (Sep 02 2017) ISSN: 1555-8576 [Electronic] United States
• PMID: 28799829 (Publication Type: Journal Article)

Chemical References

• Histones
• Smad Proteins
• Transforming Growth Factor beta1
• Ataxia Telangiectasia Mutated Proteins

Topics

• Animals
• Apoptosis (genetics)
• Ataxia Telangiectasia Mutated Proteins (metabolism)
• Carcinoma (metabolism, pathology, radiotherapy)
• Cell Cycle Checkpoints (radiation effects)
• Cell Proliferation
• Cell Survival (radiation effects)
• Disease Models, Animal
• Fluorescent Antibody Technique
• Heterografts
• Histones (metabolism)
• Humans
• Mice
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms (metabolism, pathology, radiotherapy)
• Phosphorylation
• Radiotherapy
• Signal Transduction (radiation effects)
• Smad Proteins (metabolism)
• Transforming Growth Factor beta1 (metabolism)