PIG3 downregulation enhances the radiosensitivity of NSCLC cells by promoting G2/M cell cycle arrest and apoptosis

Hao Zhou, Linfeng Tang, Zeng Fu Shang, Ping Kun Zhou, Ming Li

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)19-25
Number of pages7
JournalRadiation Medicine and Protection
Issue number1
StatePublished - Mar 2023
Externally publishedYes


  • Apoptosis
  • Cell cycle
  • Non-small cell lung cancer
  • PIG3
  • Radioresistance

ASJC Scopus subject areas

  • Emergency Medical Services
  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging
  • Public Health, Environmental and Occupational Health


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