TY - JOUR
T1 - PIG3 downregulation enhances the radiosensitivity of NSCLC cells by promoting G2/M cell cycle arrest and apoptosis
AU - Zhou, Hao
AU - Tang, Linfeng
AU - Shang, Zeng Fu
AU - Zhou, Ping Kun
AU - Li, Ming
N1 - Funding Information:
This research was funded by the National Natural Science Foundation of China ( 81673091 , 31300694 ).
Funding Information:
We would like to extend our gratitude to the Priority Academic Program Development of Jiangsu Higher Education Institutions ( PAPD ) and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection for their support during this study.
Publisher Copyright:
© 2022 Chinese Medical Association
PY - 2022
Y1 - 2022
N2 - Objective: To investigate the mechanism of p53-induced gene 3 (PIG3)-regulation of radioresistance in human non-small cell lung cancer (NSCLC) cells, in order to explore new biomarkers and therapeutic targets to combat radioresistance and improve the 5-year survival rate. Methods: The PIG3 gene was knocked down in A549 cells using siRNA, and was overexpressed in H1299 cells using a PIG3 expression plasmid. After confirming PIG3 knockdown and overexpression through the Western blot analysis, the radiosensitivity, DNA damage, cell cycle distribution, and apoptosis in these cells were analyzed using colony formation assay, immunofluorescence staining for γH2AX, and flow cytometry, respectively. Results: PIG3 silencing markedly increased the radiosensitivity of NSCLC cells, with radiosensitization ratios of 1.12 and 1.25. Compared with the corresponding negative control, PIG3 knockdown significantly enhanced G2/M phase arrest (siNC: 26.12 ± 2.50, siPIG3#1: 34.98 ± 4.19, siPIG3#2: 37.79 ± 3.53, P < 0.05), promoted radiation-induced apoptosis (siNC: 14.61 ± 1.85, siPIG3#1: 17.26 ± 1.14, siPIG3#2: 20.70 ± 2.04, P < 0.05), and reduced the number of γ-H2AX foci 0.5, 1, and 2 h after radiation (P < 0.05). Conversely, PIG3 overexpression markedly decreased the radiosensitivity of NSCLC cells, as evidenced by the reduction of G2/M phase arrest (NC: 33.18 ± 2.11 vs. PIG3: 24.21 ± 3.09, P < 0.05) and apoptosis (NC: 15.49 ± 0.56 vs. PIG3: 12.79 ± 0.29, P < 0.05), and increased DNA damage (P < 0.05). Conclusions: PIG3 downregulation increases the radiosensitivity of NSCLC cells, and PIG3-upregulation leads to the progression in radioresistance. Therefore, PIG3 is a potential target for radiotherapy for NSCLC.
AB - Objective: To investigate the mechanism of p53-induced gene 3 (PIG3)-regulation of radioresistance in human non-small cell lung cancer (NSCLC) cells, in order to explore new biomarkers and therapeutic targets to combat radioresistance and improve the 5-year survival rate. Methods: The PIG3 gene was knocked down in A549 cells using siRNA, and was overexpressed in H1299 cells using a PIG3 expression plasmid. After confirming PIG3 knockdown and overexpression through the Western blot analysis, the radiosensitivity, DNA damage, cell cycle distribution, and apoptosis in these cells were analyzed using colony formation assay, immunofluorescence staining for γH2AX, and flow cytometry, respectively. Results: PIG3 silencing markedly increased the radiosensitivity of NSCLC cells, with radiosensitization ratios of 1.12 and 1.25. Compared with the corresponding negative control, PIG3 knockdown significantly enhanced G2/M phase arrest (siNC: 26.12 ± 2.50, siPIG3#1: 34.98 ± 4.19, siPIG3#2: 37.79 ± 3.53, P < 0.05), promoted radiation-induced apoptosis (siNC: 14.61 ± 1.85, siPIG3#1: 17.26 ± 1.14, siPIG3#2: 20.70 ± 2.04, P < 0.05), and reduced the number of γ-H2AX foci 0.5, 1, and 2 h after radiation (P < 0.05). Conversely, PIG3 overexpression markedly decreased the radiosensitivity of NSCLC cells, as evidenced by the reduction of G2/M phase arrest (NC: 33.18 ± 2.11 vs. PIG3: 24.21 ± 3.09, P < 0.05) and apoptosis (NC: 15.49 ± 0.56 vs. PIG3: 12.79 ± 0.29, P < 0.05), and increased DNA damage (P < 0.05). Conclusions: PIG3 downregulation increases the radiosensitivity of NSCLC cells, and PIG3-upregulation leads to the progression in radioresistance. Therefore, PIG3 is a potential target for radiotherapy for NSCLC.
KW - Apoptosis
KW - Cell cycle
KW - Non-small cell lung cancer
KW - PIG3
KW - Radioresistance
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U2 - 10.1016/j.radmp.2022.10.003
DO - 10.1016/j.radmp.2022.10.003
M3 - Article
AN - SCOPUS:85141963770
SN - 2666-5557
JO - Radiation Medicine and Protection
JF - Radiation Medicine and Protection
ER -