Inhibition of FASN expression enhances radiosensitivity in human non-small cell lung cancer

摘要

Fatty acid synthase (FASN) is the key enzyme required for the de novo synthesis of long-chain fatty acids. FASN has been observed to be overexpressed in the majority of cancer tissues, and its expression is associated with a poor prognosis, potentially mediated by resistance to drug or radiation. The present study investigated whether the downregulation of FASN in non-small cell lung cancer (NSCLC) may increase radiosensitivity. A lentiviral vector containing short hairpin RNA targeted to FASN (pSIH-H1-Puro-shFASN) was successfully constructed and transfected into A549 cells to knockdown the gene by RNA interference. pSIH-H1-Puro-shFASN was used as the experimental group, while pSIH-H1-Puro-shGFP was used as a control group. The mRNA expression levels of FASN were determined using quantitative polymerase chain reaction. In addition, cell proliferation was measured using cell counting kit-8 assay, and colony formation assay was performed to determine the radiosensitizing effect of FASN knockdown. The cell cycle distribution and apoptotic rates were analyzed using flow cytometry, while western blot analysis was used to assess the expression of DNA-dependent protein kinase catalytic subunit protein, which is associated with DNA double-strand break (DSB) repair. The results of the present study revealed that NSCLC cells are more sensitive to radiation following the knockdown of FASN. Furthermore, the increased radiosensitivity may be associated with increased proliferation, promotion of apoptosis and cell cycle arrest in the G2/M phase. Furthermore, downregulated FASN expression reduced the levels of DNA DSB repair-associated proteins following treatment with radiation. These results indicate that silencing FASN may sensitize NSCLC cells to radiation treatment. Therefore, FASN may be a potential novel therapeutic target to improve the response of NSCLCs to radiation therapy.