Open Access

Radiosensitizing effects of Cyclocarya paliurus polysaccharide on hypoxic A549 and H520 human non-small cell lung carcinoma cells

  • Authors:
    • Fengmin Zhang
    • Bin Fan
    • Lijun Mao
  • View Affiliations

  • Published online on: July 26, 2019     https://doi.org/10.3892/ijmm.2019.4289
  • Pages: 1233-1242
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cyclocarya paliurus (CP) polysaccharide (CPP) is a chemical component contained in CP, which has been reported to possess significant hypoglycemic activity. The present study aimed to investigate the radiosensitizing effect and underlying mechanisms of CPP on hypoxic A549 and H520 human non‑small cell lung carcinoma cells. Cell viability, apoptosis and proliferation were determined using Cell Counting kit‑8 assay, flow cytometry and colony formation assay, respectively. mRNA and protein expression levels were determined by reverse transcription‑quantitative PCR and western blot analysis, respectively. The results suggested that CPP markedly inhibited the viability of hypoxic A549 and H520 cells. In response to combined treatment with CPP and radiation, hypoxic A549 and H520 cells exhibited enhanced apoptosis; in addition, cell proliferation was suppressed and the expression levels of hypoxia‑inducible factor‑1α, survivin and cleaved caspase‑3 were modified. Furthermore, CPP in combination with radiation affected the mammalian target of rapamycin (mTOR)/Akt/phosphatidylinositol‑4,5‑bisphosphate 3‑kinase (PI3K) pathway. These findings indicated that CPP may enhance the radiosensitivity of hypoxic A549 and H520 cells; this effect may be associated with inhibition of the mTOR/Akt/PI3K pathway. The potential radiosensitizing effects of CPP on hypoxic A549 and H520 cells suggested that CPP may be an effective target for treatment of non‑small cell lung carcinoma.

References

1 

Giroux Leprieur E, Dumenil C, Julie C, Giraud V, Dumoulin J, Labrune S and Chinet T: Immunotherapy revolutionises non-small-cell lung cancer therapy: Results, perspectives and new challenges. Eur J Cancer. 78:16–23. 2017. View Article : Google Scholar : PubMed/NCBI

2 

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI

4 

Garrison GW: Lung cancer screening. Cancer Cytopathol. 124:533–534. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Remon J, Besse B and Soria JC: Successes and failures: What did we learn from recent first-line treatment immunotherapy trials in non-small cell lung cancer? BMC Med. 15:552017. View Article : Google Scholar : PubMed/NCBI

6 

Masters GA, Temin S, Azzoli CG, Giaccone G, Baker S Jr, Brahmer JR, Ellis PM, Gajra A, Rackear N, Schiller JH, et al: Systemic therapy for stage IV non-small-cell lung cancer: American society of clinical oncology clinical practice guideline update. J Clin Oncol. 33:3488–3515. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Bjørnetrø T, Handeland KR, Meltzer S, Samiappan R, Lyckander LG, Jegerschöld C, Sønstevold L, Thusyanthan NS, Redalen KR and Ree AH: Low release of exosomal miR-663a from hypoxic tumor cells and poor tumor response to neoadjuvant radiotherapy in rectal cancer patients. Cancer Res. 77:45142017.

8 

Horsman MR and Overgaard J: The impact of hypoxia and its modification of the outcome of radiotherapy. J Radiat Res. 57(Suppl 1): i90–i98. 2016. View Article : Google Scholar : PubMed/NCBI

9 

Song G, Ji C, Liang C, Song X, Yi X, Dong Z, Yang K and Liu Z: TaOx decorated perfluorocarbon nanodroplets as oxygen reservoirs to overcome tumor hypoxia and enhance cancer radiotherapy. Biomaterials. 112:257–263. 2017. View Article : Google Scholar

10 

Bonnet M, Hong CR, Wong WW, Liew LP, Shome A, Wang J, Gu Y, Stevenson RJ, Qi W, Anderson RF, et al: Next-generation hypoxic cell radiosensitizers: Nitroimidazole alkylsulfonamides. J Med Chem. 61:1241–1254. 2018. View Article : Google Scholar

11 

Xiao HT, Wen B, Ning ZW, Zhai LX, Liao CH, Lin CY, Mu HX and Bian ZX: Cyclocarya paliurus tea leaves enhances pancreatic β cell preservation through inhibition of apoptosis. Sci Rep. 7:91552017. View Article : Google Scholar

12 

Xie JH, Xie MY, Nie SP, Shen MY, Wang YX and Li C: Isolation, chemical composition and antioxidant activities of a water-soluble polysaccharide from Cyclocarya paliurus (Batal.) Iljinskaja. Food Chem. 119:1626–1632. 2010. View Article : Google Scholar

13 

Xie JH, Liu X, Shen MY, Nie SP, Zhang H, Li C, Gong DM and Xie MY: Purification, physicochemical characterisation and anticancer activity of a polysaccharide from Cyclocarya paliurus leaves. Food Chem. 136:1453–1460. 2013. View Article : Google Scholar

14 

Li S, Li J, Guan XL, Li J, Deng SP, Li LQ, Tang MT, Huang JG, Chen ZZ and Yang RY: Hypoglycemic effects and constituents of the barks of Cyclocarya paliurus and their inhibiting activities to glucosidase and glycogen phosphorylase. Fitoterapia. 82:1081–1085. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Lu CX and Cheng BQ: Radiosensitizing effects of Lycium barbarum polysaccharide for Lewis lung cancer. Zhong Xi Yi Jie He Za Zhi. 11:611–612. 5821991.In Chinese.

16 

Meng X, Grötsch B, Luo Y, Knaup KX, Wiesener MS, Chen XX, Jantsch J, Fillatreau S, Schett G and Bozec A: Hypoxia-inducible factor-1α is a critical transcription factor for IL-10-producing B cells in autoimmune disease. Nat Commun. 9:2512018. View Article : Google Scholar

17 

Szalowska E, Stoopen G, Rijk JC, Wang S, Hendriksen PJ, Groot MJ, Ossenkoppele J and Peijnenburg AA: Effect of oxygen concentration and selected protocol factors on viability and gene expression of mouse liver slices. Toxicol In Vitro. 27:1513–1524. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Zou K, Tong E, Xu Y, Deng X and Zou L: Down regulation of mammalian target of rapamycin decreases HIF-1α and survivin expression in anoxic lung adenocarcinoma A549 cell to elemene and/or irradiation. Tumour Biol. 35:9735–9741. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Peery RC, Liu JY and Zhang JT: Targeting survivin for therapeutic discovery: Past, present, and future promises. Drug Discov Today. 22:1466–1477. 2017. View Article : Google Scholar : PubMed/NCBI

20 

Nakahara T, Morita A, Yagasaki R, Mori A and Sakamoto K: Mammalian target of rapamycin (mTOR) as a potential therapeutic target in pathological ocular angiogenesis. Biol Pharm Bull. 40:2045–2049. 2017. View Article : Google Scholar : PubMed/NCBI

21 

Bahrami A, Hasanzadeh M, Hassanian SM, ShahidSales S, Ghayour-Mobarhan M, Ferns GA and Avan A: The potential value of the PI3K/Akt/mTOR signaling pathway for assessing prognosis in cervical cancer and as a target for therapy. J Cell Biochem. 118:4163–4169. 2017. View Article : Google Scholar : PubMed/NCBI

22 

Cao ZX, Yang YT, Yu S, Li YZ, Wang WW, Huang J, Xie XF, Xiong L, Lei S and Peng C: Pogostone induces autophagy and apoptosis involving PI3K/Akt/mTOR axis in human colorectal carcinoma HCT116 cells. J Ethnopharmacol. 202:20–27. 2017. View Article : Google Scholar

23 

Oh TI, Lee YM, Nam TJ, Ko YS, Mah S, Kim J, Kim Y, Reddy RH, Kim YJ, Hong S and Lim JH: Fascaplysin exerts anti-cancer effects through the downregulation of survivin and HIF-1α and inhibition of VEGFR2 and TRKA. Int J Mol Sci. 18:pii: E20742017. View Article : Google Scholar

24 

Wang Z, Xie J, Yang Y, Zhang F, Wang S, Wu T, Shen M and Xie M: Sulfated Cyclocarya paliurus polysaccharides markedly attenuates inflammation and oxidative damage in lipopolysaccharide-treated macrophage cells and mice. Sci Rep. 7:404022017. View Article : Google Scholar : PubMed/NCBI

25 

Cheki M, Shirazi A, Mahmoudzadeh A, Bazzaz JT and Hosseinimehr SJ: The radioprotective effect of metformin against cytotoxicity and genotoxicity induced by ionizing radiation in cultured human blood lymphocytes. Mutat Res. 809:24–32. 2016. View Article : Google Scholar : PubMed/NCBI

26 

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

27 

Her S, Jaffray DA and Allen C: Gold nanoparticles for applications in cancer radiotherapy: Mechanisms and recent advancements. Adv Drug Deliv Rev. 109:84–101. 2017. View Article : Google Scholar

28 

Weichselbaum RR, Liang H, Deng L and Fu YX: Radiotherapy and immunotherapy: A beneficial liaison? Nat Rev Clin Oncol. 14:365–379. 2017. View Article : Google Scholar : PubMed/NCBI

29 

Garcia-Aranda M, Téllez T, Muñoz M and Redondo M: Clusterin inhibition mediates sensitivity to chemotherapy and radiotherapy in human cancer. Anticancer Drugs. 28:702–716. 2017. View Article : Google Scholar : PubMed/NCBI

30 

Guo Y, Sun W, Gong T, Chai Y, Wang J, Hui B, Li Y, Song L and Gao Y: miR-30a radiosensitizes non-small cell lung cancer by targeting ATF1 that is involved in the phosphorylation of ATM. Oncol Rep. 37:1980–1988. 2017. View Article : Google Scholar : PubMed/NCBI

31 

Wang J, Wang Y, Mei H, Yin Z, Geng Y, Zhang T, Wu G and Lin Z: The BET bromodomain inhibitor JQ1 radiosensitizes non-small cell lung cancer cells by upregulating p21. Cancer Lett. 391:141–151. 2017. View Article : Google Scholar : PubMed/NCBI

32 

Wang H, Mu X, He H and Zhang XD: Cancer radiosensitizers. Trends Pharmacol Sci. 39:24–48. 2018. View Article : Google Scholar

33 

Xu H, Sun G, Wang H, Yue Q, Tang H and Wu Q: Dynamic observation of the radiosensitive effect of irisquinone on rabbit VX2 lung transplant tumors by using fluorine-18-deoxyglucose positron emission tomography/computed tomography. Nucl Med Commun. 34:220–228. 2013. View Article : Google Scholar : PubMed/NCBI

34 

Brown JM and Le QT: Tumor hypoxia is important in radiotherapy, but how should we measure it? Int J Radiat Oncol Biol Phys. 54:1299–1301. 2002. View Article : Google Scholar : PubMed/NCBI

35 

Toffoli S and Michiels C: Intermittent hypoxia is a key regulator of cancer cell and endothelial cell interplay in tumours. FEBS J. 275:2991–3002. 2008. View Article : Google Scholar : PubMed/NCBI

36 

Bruick RK and Mcknight SL: A conserved family of prolyl-4-hydroxylases that modify HIF. Science. 294:1337–1340. 2001. View Article : Google Scholar : PubMed/NCBI

37 

Berra E, Roux D, Richard DE and Pouysségur J: Hypoxia-inducible factor-1 alpha (HIF-1 alpha) escapes O(2)-driven proteasomal degradation irrespective of its subcellular localization: Nucleus or cytoplasm. EMBO Rep. 2:615–620. 2001. View Article : Google Scholar : PubMed/NCBI

38 

Jaakkola P, Mole DR, Tian YM, Wilson MI, Gielbert J, Gaskell SJ, von Kriegsheim A, Hebestreit HF, Mukherji M, Schofield CJ, et al: Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science. 292:468–472. 2001. View Article : Google Scholar : PubMed/NCBI

39 

Wouters BG and Koritzinsky M: Hypoxia signalling through mTOR and the unfolded protein response in cancer. Nat Rev Cancer. 8:851–864. 2008. View Article : Google Scholar : PubMed/NCBI

40 

Rödel F, Hoffmann J, Distel L, Herrmann M, Noisternig T, Papadopoulos T, Sauer R and Rödel C: Survivin as a radioresistance factor, and prognostic and therapeutic target for radiotherapy in rectal cancer. Cancer Res. 65:4881–4887. 2005. View Article : Google Scholar : PubMed/NCBI

41 

Han C, Nie SP, Huang DF, Chen YQ, Xie JH and Xie MY: Effects of polysaccharides from Cyclocarya paliurus (Batal.) Iljinskjk on growth of MGC803 Cells. Nat Prod Res Dev. 21:952–955. 2009.

42 

Xie JH, Wang ZJ, Shen MY, Nie SP, Gong B, Li HS, Zhao Q, Li WJ and Yang G: Sulfated modification, characterization and antioxidant activities of polysaccharide from Cyclocarya paliurus. Food Hydrocoll. 53:7–15. 2016. View Article : Google Scholar

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October 2019
Volume 44 Issue 4

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APA
Zhang, F., Fan, B., & Mao, L. (2019). Radiosensitizing effects of Cyclocarya paliurus polysaccharide on hypoxic A549 and H520 human non-small cell lung carcinoma cells. International Journal of Molecular Medicine, 44, 1233-1242. https://doi.org/10.3892/ijmm.2019.4289
MLA
Zhang, F., Fan, B., Mao, L."Radiosensitizing effects of Cyclocarya paliurus polysaccharide on hypoxic A549 and H520 human non-small cell lung carcinoma cells". International Journal of Molecular Medicine 44.4 (2019): 1233-1242.
Chicago
Zhang, F., Fan, B., Mao, L."Radiosensitizing effects of Cyclocarya paliurus polysaccharide on hypoxic A549 and H520 human non-small cell lung carcinoma cells". International Journal of Molecular Medicine 44, no. 4 (2019): 1233-1242. https://doi.org/10.3892/ijmm.2019.4289