International Journal of Radiation Research
نشریه پرتو پژوه
Int J Radiat Res
Basic Sciences
http://ijrr.com
79
journal79
2322-3243
2345-4229
10.61186/ijrr
en
jalali
1399
7
1
gregorian
2020
10
1
18
4
online
1
fulltext
en
ATM induces radioresistance of non-small cell lung cancer A549 cells by downregulation of MDMX
Medical Physics
Medical Physics
تحقيق بديع
Original Research
<div style="text-align: justify;">Background: Tumor radioresistance leads to a reduction in the efficiency of radiation therapy. It is very important to explore the cellular mechanisms leading to radioresistance and to find potential therapeutic targets, which might improve the efficacy of radiation therapy. This study was to investigate the role of ataxia-telangiectasia mutated (ATM) and murine double minute X (MDMX) in radioresistance in non-small cell lung cancer A549 cells and their corresponding mechanisms of action. Materials and Methods: Non-small cell lung cancer A549 cells were irradiated with X-rays in the presence or absence of ATM inhibitor. Cell survival, cell apoptosis, cell proliferation, mRNA of ATM and MDMX, and protein expression of ATM, MDMX, γ-H2AX, Caspase3, and Beclin1 were measured. Results: After the inhibitor (KU60019) treatment combined with X irradiation, the A549 cells showed a significant decrease in colony formations compared to the group received irradiation alone. The MDMX knockdown A549 cells showed a significant increase in colony formations compared to the control group. ATM downregulated the expression of MDMX after irradiation treatment in A549 cells. Irradiation led to a significant increase in γ-H2AX expression, but MDMX knockdown decreased the γ-H2AX expression after irradiation. The change of Caspase3 expression was the same as γ-H2AX. Irradiation led to a significant increase of Beclin1 expression and MDMX knockdown increased the Beclin1 expression after irradiation. Conclusion: This study indicated that ATM induced radioresistance through downregulating the expression of MDMX, which was at least partly associated with the activation of autophagy and the decrease of DNA damage in A549 cells.</div>
ATM, MDMX, radioresistance, non-small cell lung cancer.
835
840
http://ijrr.com/browse.php?a_code=A-10-2055-70&slc_lang=en&sid=1
R.
Xing
7900319475328460017389
7900319475328460017389
No
Department of Clinical Oncology, Shengjing Hospital of China Medical University, Shenyang, China
J.J.
Chen
7900319475328460017390
7900319475328460017390
No
Department of Clinical Oncology, Shengjing Hospital of China Medical University, Shenyang, China
M.Y.
Chen
7900319475328460017391
7900319475328460017391
No
Department of Clinical Oncology, Shengjing Hospital of China Medical University, Shenyang, China
J.
Lian
7900319475328460017392
7900319475328460017392
No
Department of Clinical Oncology, Shengjing Hospital of China Medical University, Shenyang, China
L.F.
Li
7900319475328460017393
7900319475328460017393
No
Department of Clinical Oncology, Shengjing Hospital of China Medical University, Shenyang, China
X.
Zhou
7900319475328460017394
7900319475328460017394
No
Department of Clinical Oncology, Shengjing Hospital of China Medical University, Shenyang, China
R.Q.
Liu
7900319475328460017395
7900319475328460017395
No
Department of Clinical Oncology, Shengjing Hospital of China Medical University, Shenyang, China
Y.Z.
Xie
7900319475328460017396
7900319475328460017396
No
Department of Clinical Oncology, Shengjing Hospital of China Medical University, Shenyang, China
W.
Huang
7900319475328460017397
7900319475328460017397
No
Department of Clinical Oncology, Shengjing Hospital of China Medical University, Shenyang, China
H.
Zhao
7900319475328460017398
7900319475328460017398
No
Department of Clinical Oncology, Shengjing Hospital of China Medical University, Shenyang, China
Y.C.
Zeng
wellyy2005@hotmail.com
7900319475328460017399
7900319475328460017399
Yes
Department of Medical Oncology, Cancer Center, The Second Affiliated Hospital of Hainan Medical University, Haikou, China.