Open AccessSALL 4 induces radioresistance in nasopharyngeal carcinoma via the ATM /Chk2/p53 pathway
Author(s) -
Nie Xin,
Guo Ergang,
Wu Cheng,
Liu Dongbo,
Sun Wei,
Zhang Linli,
Long Guoxian,
Mei Qi,
Wu Kongming,
Xiong Huihua,
Hu Guoqing
Publication year - 2019
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.2056
Subject(s) - radioresistance , nasopharyngeal carcinoma , gene knockdown , apoptosis , radiosensitivity , cancer research , downregulation and upregulation , biology , gene silencing , radiation therapy , cell culture , medicine , genetics , gene
Radiotherapy is the mainstay and primary curative treatment modality in nasopharyngeal carcinoma ( NPC ), whose efficacy is limited by the development of intrinsic and acquired radioresistance. Thus, deciphering new molecular targets and pathways is essential for enhancing the radiosensitivity of NPC . SALL 4 is a vital factor in the development and prognosis of various cancers, but its role in radioresistance remains elusive. This study aimed to explore the association of SALL 4 expression with radioresistance of NPC . It was revealed that SALL 4 expression was closely correlated with advanced T classification of NPC patients. Inhibition of SALL 4 reduced proliferation and sensitized cells to radiation both in vitro and in vivo. Furthermore, SALL 4 silencing increased radiation‐induced DNA damage, apoptosis, and G2/M arrest in CNE 2 and CNE 2R cells. Moreover, knockdown of SALL 4 impaired the expression of p‐ ATM , p‐Chk2, p‐p53, and anti‐apoptosis protein Bcl‐2, while pro‐apoptosis protein was upregulated. These findings indicate that SALL 4 could induce radioresistance via ATM /Chk2/p53 pathway and its downstream proteins related to apoptosis. Targeting SALL 4 might be a promising approach for the development of novel radiosensitizing therapeutic agents for radioresistant NPC patients.