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Article

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

  • Authors:
    • Ning Zhan
    • Bin Li
    • Xiangying Xu
    • Jianyu Xu
    • Songliu Hu
  • View Affiliations / Copyright

    Affiliations: Department of Radiation Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China, Department of Plastic Surgery, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, The Center Laboratory of Radiobiology, Institute of Cancer Prevention and Treatment of Heilongjiang Province, Harbin, Heilongjiang 150081, P.R. China
  • Pages: 4578-4584
    |
    Published online on: January 29, 2018
       https://doi.org/10.3892/ol.2018.7896
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Abstract

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.
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1 

Takanen S, Bangrazi C, Graziano V, Parisi A, Resuli B, Simione L, Caiazzo R, Raffetto N and Tombolini V: Number of mediastinal lymph nodes as a prognostic factor in PN2 non small cell lung cancer: A single centre experience and review of the literature. Asian Pac J Cancer Prev. 15:7559–7562. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Tarone RE: On the International Agency for Research on Cancer classification of glyphosate as a probable human carcinogen. Eur J Cancer Prev. Nov 8–2017.(Epub ahead of print).

3 

Parsons A, Daley A, Begh R and Aveyard P: Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: Systematic review of observational studies with meta-analysis. BMJ. 340:b55692010. View Article : Google Scholar : PubMed/NCBI

4 

Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer Clin. 61:69–90. 2011. View Article : Google Scholar

5 

Fernandes AT, Mitra N, Xanthopoulos E, Evans T, Stevenson J, Langer C, Kucharczuk JC, Lin L and Rengan R: The impact of extent and location of mediastinal lymph node involvement on survival in Stage III non-small cell lung cancer patients treated with definitive radiotherapy. Int J Radiat Oncol Biol Phys. 83:340–347. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Shikazono N, Noguchi M, Fujii K, Urushibara A and Yokoya A: The yield, processing, and biological consequences of clustered DNA damage induced by ionizing radiation. J Radiat Res. 50:27–36. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Greenstein JP: Biochemistry of cancer. New York: Academic Press; 1954

8 

Nakashima RA, Paggi MG and Pedersen PL: Contributions of glycolysis and oxidative phosphorylation to adenosine 5′-triphosphate production in AS-30D hepatoma cells. Cancer Res. 44:5702–5706. 1984.PubMed/NCBI

9 

Medes G, Thomas A and Weinhouse S: Metabolism of neoplastic tissue. IV. A study of lipid synthesis in neoplastic tissue slices in vitro. Cancer Res. 13:27–29. 1953.PubMed/NCBI

10 

Chung YW, Han DS, Park YK, Son BK, Paik CH, Lee HL, Jeon YC and Sohn JH: Association of obesity, serum glucose and lipids with the risk of advanced colorectal adenoma and cancer: a case-control study in Korea. Dig Liver Dis. 38:668–672. 2006. View Article : Google Scholar : PubMed/NCBI

11 

Williams RR, Shorlie PD and Feinleib M: Cancer incidence by levels of cholesterol. JAMA. 245:247–25234. 1981. View Article : Google Scholar : PubMed/NCBI

12 

Liu H, Liu JY, Wu X and Zhang JT: Biochemistry, molecular biology, and pharmacology of fatty acid synthase, an emerging therapeutic target and diagnosis/prognosis marker. Int J Biochem Mol Biol. 1:69–89. 2010.PubMed/NCBI

13 

Khan A, Aljarbou AN, Aldebasi YH, Faisal SM and Khan MA: Resveratro suppresses the proliferation of breast cancer cells by inhibiting fatty acid synthase signaling pathway. Cancer Epidemiol. 38:765–772. 2014. View Article : Google Scholar : PubMed/NCBI

14 

Jiang B, Li EH, Lu YY, Jiang Q, Cui D, Jing YF and Xia SJ: Inhibition of fatty acid synthase supresses P-akt and induces apoptosis in bladder cancer. Urology. 80:484.e9–e15

15 

Kao YC, Lee SW, Lin LC, Chen LT, Hsing CH, Hsu HP, Huang HY, Shiue YL, Chen TJ and Li CF: Fatty acid synthase overexpression confers an independent prognosticator and associates with radiation resistance in nasopharyngeal carcinoma. Tumor Biol. 34:759–768. 2013. View Article : Google Scholar

16 

Zhou Y, Niu C, Li Y, Gao B, Zheng J, Guo X and Ma W: Fatty acid synthase expression and esophageal cancer. Mol Biol Rep. 39:9733–9739. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Yang Y, Liu H, Li Z, Zhao Z, Yip-Schneider M, Fan Q, Schmidt CM, Chiorean EG, Xie J, Cheng L, et al: Role of fatty acid synthase in gemcitabin and radiation resistance of pancreatic cancer. Int J Biochem Mol Biol. 2:89–98. 2011.PubMed/NCBI

18 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

19 

Menendez JA and Lupu R: Fatty acid synthase and the lipogenic phenotype in cancer. Nat Rev Cancer. 7:763–77. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Shaw RJ: Glucose metabolism and cancer. Curr Opin Cell Biol. 18:598–608. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Kuhajda FP: Fatty-acid Synthase and human cancer: New perspectives on its role in tumor biology. Nutrition. 16:202–208. 2000. View Article : Google Scholar : PubMed/NCBI

22 

Smith S, Witkowski A and Joshi AK: Structural and functional organization of the animal fatty acid synthase. Prog Lipid Res. 42:289–317. 2003. View Article : Google Scholar : PubMed/NCBI

23 

Pizer ES, Thupari J, Han WF, Pinn ML, Chrest FJ, Frehywot GL, Townsend CA and Kuhajda FP: Malonyl-coenzyme-A is a potential mediator of cytotoxicity induced by fatty-acid synthase inhibition in human breast cancer cells and xenografts. Cancer Res. 60:213–218. 2000.PubMed/NCBI

24 

De Schrijver E, Brusselmans K, Heyns W, Verhoeven G and Swinnen JV: RNA interference-mediated silencing of the fatty acid synthase gene attenuates growth and induces morphological changes and apoptosis of LNCaP prostate cancer cells. Cancer Res. 63:3799–3804. 2003.PubMed/NCBI

25 

Yoshii Y, Furukawa T, Oyama N, Hasegawa Y, Kiyono Y, Nishii R, Waki A, Tsuji AB, Sogawa C, Wakizaka H, et al: Fatty acid synthase is a key target in multiple essential tumor functions of prostate cancer: Uptake of radiolabeled acetate as a predictor of the targeted therapy outcome. PLoS One. 8:e645702013. View Article : Google Scholar : PubMed/NCBI

26 

Liu H, Wu X, Dong Z, Luo Z, Zhao Z, Xu Y and Zhang JT: Fatty acid synthase causes drug resistance by inhibiting TNF-α and ceramide production. J Lipid Res. 54:776–785. 2013. View Article : Google Scholar : PubMed/NCBI

27 

Yanold J: Molecular aspects of cellular responses to radiotherapy. Radiothery Oncol. 44:1–7. 1997. View Article : Google Scholar

28 

Thompson LH: Evidence that mammalian cells possess homologous recombinational repair pathways. Mutat Res. 363:77–88. 1996. View Article : Google Scholar : PubMed/NCBI

29 

Bertolini LR, Bertolini M, Anderson GB, Maga EA, Madden KR and Murray JD: Transient depletion of Ku70 and Xrcc4 by RNAi as a means to manipulate the non-homologous end-joining pathway. J Biotechnol. 128:246–257. 2007. View Article : Google Scholar : PubMed/NCBI

30 

Hamer G, Roepers Gajadien HL, Van Duyn-Goedhart A, Gademan IS, Kal HB, van Buul PP, Ashley T and de Rooij DG: Function of DNA-protein kinase catalytic subunit during the early meiotic prophase without Ku70 and Ku86. Biol Reprod. 68:717–721. 2003. View Article : Google Scholar : PubMed/NCBI

31 

Jeggo PA: Identification of genes involved in repair of DNA doublestrand breaks in mammary cells. Radiat Res. 150:580–591. 1998. View Article : Google Scholar

32 

Yaneva M, Kowalewski T and Lieber MR: Interaction of DNA-dependent protein kinase with DNA and with Ku: Biochemical and atomic force microscopy. EMBO J. 16:5098–5112. 1997. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhan N, Li B, Xu X, Xu J and Hu S: Inhibition of FASN expression enhances radiosensitivity in human non-small cell lung cancer. Oncol Lett 15: 4578-4584, 2018.
APA
Zhan, N., Li, B., Xu, X., Xu, J., & Hu, S. (2018). Inhibition of FASN expression enhances radiosensitivity in human non-small cell lung cancer. Oncology Letters, 15, 4578-4584. https://doi.org/10.3892/ol.2018.7896
MLA
Zhan, N., Li, B., Xu, X., Xu, J., Hu, S."Inhibition of FASN expression enhances radiosensitivity in human non-small cell lung cancer". Oncology Letters 15.4 (2018): 4578-4584.
Chicago
Zhan, N., Li, B., Xu, X., Xu, J., Hu, S."Inhibition of FASN expression enhances radiosensitivity in human non-small cell lung cancer". Oncology Letters 15, no. 4 (2018): 4578-4584. https://doi.org/10.3892/ol.2018.7896
Copy and paste a formatted citation
x
Spandidos Publications style
Zhan N, Li B, Xu X, Xu J and Hu S: Inhibition of FASN expression enhances radiosensitivity in human non-small cell lung cancer. Oncol Lett 15: 4578-4584, 2018.
APA
Zhan, N., Li, B., Xu, X., Xu, J., & Hu, S. (2018). Inhibition of FASN expression enhances radiosensitivity in human non-small cell lung cancer. Oncology Letters, 15, 4578-4584. https://doi.org/10.3892/ol.2018.7896
MLA
Zhan, N., Li, B., Xu, X., Xu, J., Hu, S."Inhibition of FASN expression enhances radiosensitivity in human non-small cell lung cancer". Oncology Letters 15.4 (2018): 4578-4584.
Chicago
Zhan, N., Li, B., Xu, X., Xu, J., Hu, S."Inhibition of FASN expression enhances radiosensitivity in human non-small cell lung cancer". Oncology Letters 15, no. 4 (2018): 4578-4584. https://doi.org/10.3892/ol.2018.7896
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