Zheng Zexuan,Shen Jiahao,Pei Hailong,et al.PLIN5 enhances radioresistance in non-small cell lung cancer cells by mediating the accumulation of lipid droplets[J].Chinese Journal of Radiological Medicine and Protection,2026,46(5):483-489
PLIN5 enhances radioresistance in non-small cell lung cancer cells by mediating the accumulation of lipid droplets
Received:September 18, 2025  
DOI:10.3760/cma.j.cn112271-20250918-00336
KeyWords:Perilipin 5  Neutral lipids  Non-small cell lung cancer  Radiosensitivity
FundProject:国家自然科学基金(82273578)
Author NameAffiliationE-mail
Zheng Zexuan School of Radiation Medicine and Protection, Suzhou Medical College of Soochow University, Suzhou 215123, China  
Shen Jiahao School of Radiation Medicine and Protection, Suzhou Medical College of Soochow University, Suzhou 215123, China  
Pei Hailong School of Radiation Medicine and Protection, Suzhou Medical College of Soochow University, Suzhou 215123, China  
Li Wanshi Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310022, China liws@zjcc.org.cn 
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Abstract::
      Objective To investigate the effect of perilipin 5 (PLIN5) on neutral lipid content and radiosensitivity in non-small cell lung cancer (NSCLC) cells and its underlying mechanism. Methods The NSCLC cell line A549 was irradiated with 0 or 2 Gy of X-rays. PLIN5 gene expression levels in the two groups were detected via differential gene expression analysis and quantitative real-time PCR (qPCR). Cell lines stably overexpressing full-length PLIN5 or a truncated mutant lacking the lipid-binding domain, as well as PLIN5 knockdown cell lines, were constructed. Wild-type cells and empty vector-transfected cells served as controls. These cell groups were irradiated with 0 Gy or 8 Gy of X-rays. Relative cell proliferation rate curve and cell apoptosis was assessed. At 24 h post-irradiation, cells were stained with BODIPY 594 and Hoechst, and observed under a confocal microscope to evaluate lipid expression levels. Results After 2 Gy X-ray irradiation, 487 differentially expressed genes were identified in A549 cells. qPCR validation showed that PLIN5 expression increased by 2.5-fold compared to the control group (t=3.06, P<0.05). Following 8 Gy irradiation, lipid expression levels were higher in the full-length PLIN5 overexpression group and lower in the PLIN5 knockdown group compared to wild-type cells. The truncated mutant lacking the lipid-binding domain showed no significant change in lipid content. Compared with the cell viability of (1.69±0.49)% in the empty vector irradiation group, the cell viability of the PLIN5 full-length overexpression group increased to (2.49±0.92)% (t=2.64, P<0.05). Compared with the cell viability of (2.54±0.80)% in the negative control exposure group, the cell viability of the PLIN5 interference group decreased to (1.89±0.45)% (t=3.76, P<0.05). No statistically significant difference was observed among the truncated mutant transfection group, wild-type cells, and the empty vector transfection group. Conclusions Under irradiation, up-regulated PLIN5 elevates lipid content in A549 cells, thereby enhancing their radioresistance and providing evidence that lipid-metabolic reprogramming is a critical determinant of tumor cell radioresistance.
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