Ganoderma lucidum polysaccharide enhances radiosensitivity of hepatocellular carcinoma cell line HepG2 through Akt signaling pathway

Yu,Yang; Qian,Liqi; Du,Nan; Liu,Yuxiao; Zhao,Xiao; Zhang,Xin

doi:10.3892/etm.2017.5340

Ganoderma lucidum polysaccharide enhances radiosensitivity of hepatocellular carcinoma cell line HepG2 through Akt signaling pathway

Authors:
- Yang Yu
- Liqi Qian
- Nan Du
- Yuxiao Liu
- Xiao Zhao
- Xin Zhang
View Affiliations

Affiliations: Department of Traditional Chinese Medicine, The First Affiliated Hospital of the General Hospital of The People's Liberation Army of China, Beijing 100048, P.R. China, Department of Oncology, The First Affiliated Hospital of the General Hospital of The People's Liberation Army of China, Beijing 100048, P.R. China, Department of Neurosurgery, The First Affiliated Hospital of the General Hospital of The People's Liberation Army of China, Beijing 100048, P.R. China, Department of Medical administration, The First Affiliated Hospital of the General Hospital of The People's Liberation Army of China, Beijing 100048, P.R. China, Department of Pharmacy, The First Affiliated Hospital of the General Hospital of The People's Liberation Army of China, Beijing 100048, P.R. China
Published online on: October 18, 2017 https://doi.org/10.3892/etm.2017.5340
Pages: 5903-5907
Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Ganoderma lucidum polysaccharide (GLP) is a well‑known traditional Chinese medicine, known for its anti‑cancer and immunomodulatory properties. The present study aims to investigate whether GLP has a therapeutic effect on hepatocellular carcinoma (HCC) cells exposed to radiation. Immunofluorescence was used to detect the nuclei, the protein expression was measured by western blot analysis and flow cytometry was used to detect the rate of cell apoptosis. GLP treatment was demonstrated to enhance radiation‑induced growth inhibition and apoptotic death of HCC cells. At a molecular level, GLP suppressed the activities of DNA repair‑associated proteins including ataxia‑telangiectasia mutated (ATM) and DNA dependent‑protein kinase (DNA‑PK) in liver cancer cells under radiation conditions. Furthermore, the addition of an Akt inhibitor elevated the activities of DNA‑PK and ATM and attenuated the GLP‑induced HepG2 cell injury under the radiation condition. In conclusion, the present study demonstrates that GLP enhances the radiosensitivity of HCC cells via the regulation of Akt signaling pathways, implying a potential therapeutic effect of GLP as a radiation sensitizer in HCC treatment.

View Figures

View References

1	McGlynn KA, Petrick JL and London WT: Global epidemiology of hepatocellular carcinoma: An emphasis on demographic and regional variability. Clin Liver Dis. 19:223–238. 2015. View Article : Google Scholar : PubMed/NCBI
2	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
3	Lau WY and Lai EC: Hepatocellular carcinoma: Current management and recent advances. Hepatobiliary Pancreat Dis Int. 7:237–257. 2008.PubMed/NCBI
4	Xu Z, Chen X, Zhong Z, Chen L and Wang Y: Ganoderma lucidum polysaccharides: Immunomodulation and potential anti-tumor activities. Am J Chin Med. 39:15–27. 2011. View Article : Google Scholar : PubMed/NCBI
5	Guo L, Xie J, Ruan Y, Zhou L, Zhu H, Yun X, Jiang Y, Lü L, Chen K, Min Z, et al: Characterization and immunostimulatory activity of a polysaccharide from the spores of Ganoderma lucidum. Int Immunopharmacol. 9:1175–1182. 2009. View Article : Google Scholar : PubMed/NCBI
6	Lin ZB and Zhang HN: Anti-tumor and immunoregulatory activities of Ganoderma lucidum and its possible mechanisms. Acta pharmacologica Sinica. 25:1387–1395. 2004.PubMed/NCBI
7	Zhou X, Lin J, Yin Y, Zhao J, Sun X and Tang K: Ganodermataceae: Natural products and their related pharmacological functions. Am J Chin Med. 35:559–574. 2007. View Article : Google Scholar : PubMed/NCBI
8	Liu ZL, Zhu WR, Zhou WC, Ying HF, Zheng L, Guo YB, Chen JX and Shen XH: Traditional Chinese medicinal herbs combined with epidermal growth factor receptor tyrosine kinase inhibitor for advanced non-small cell lung cancer: A systematic review and meta-analysis. J Integr Med. 12:346–358. 2014. View Article : Google Scholar : PubMed/NCBI
9	Jia L, Ma S, Hou X, Wang X, Qased AB, Sun X, Liang N, Li H, Yi H, Kong D, et al: The synergistic effects of traditional Chinese herbs and radiotherapy for cancer treatment. Oncol Lett. 5:1439–1447. 2013.PubMed/NCBI
10	Yang L, Wei DD, Chen Z, Wang JS and Kong LY: Reversal effects of traditional Chinese herbs on multidrug resistance in cancer cells. Nat Prod Res. 25:1885–1889. 2011. View Article : Google Scholar : PubMed/NCBI
11	Sun Z, Huang K, Fu X, Zhou Z, Cui Y and Li H: A chemically sulfated polysaccharide derived from Ganoderma lucidum induces mitochondrial-mediated apoptosis in human osteosarcoma MG63 cells. Tumour Biol. 35:9919–9926. 2014. View Article : Google Scholar : PubMed/NCBI
12	Tie L, Yang HQ, An Y, Liu SQ, Han J, Xu Y, Hu M, Li WD, Chen AF, Lin ZB and Li XJ: Ganoderma lucidum polysaccharide accelerates refractory wound healing by inhibition of mitochondrial oxidative stress in type 1 diabetes. Cell Physiol Biochem. 29:583–594. 2012. View Article : Google Scholar : PubMed/NCBI
13	Pillai TG, Maurya DK, Salvi VP, Janardhanan KK and Nair CK: Fungal beta glucan protects radiation induced DNA damage in human lymphocytes. Ann Transl Med. 2:132014.PubMed/NCBI
14	Zeng G, Shen H, Tang G, Cai X, Bi L, Sun B, Yang Y and Xun W: A polysaccharide from the alkaline extract of Glycyrrhiza inflata induces apoptosis of human oral cancer SCC-25 cells via mitochondrial pathway. Tumour Biol. 36:6781–6788. 2015. View Article : Google Scholar : PubMed/NCBI
15	Korwek Z, Sewastianik T, Bielak-Zmijewska A, Mosieniak G, Alster O, Moreno-Villanueva M, Burkle A and Sikora E: Inhibition of ATM blocks the etoposide-induced DNA damage response and apoptosis of resting human T cells. DNA Repair (Amst). 11:864–873. 2012. View Article : Google Scholar : PubMed/NCBI
16	de Moraes Nestal G, Bella L, Zona S, Burton MJ and Lam EW: Insights into a Critical Role of the FOXO3a-FOXM1 Axis in DNA Damage Response and Genotoxic Drug Resistance. Curr Drug Targets. 17:164–177. 2016. View Article : Google Scholar : PubMed/NCBI
17	Liu S, Opiyo SO, Manthey K, Glanzer JG, Ashley AK, Amerin C, Troksa K, Shrivastav M, Nickoloff JA and Oakley GG: Distinct roles for DNA-PK, ATM and ATR in RPA phosphorylation and checkpoint activation in response to replication stress. Nucleic Acids Res. 40:10780–10794. 2012. View Article : Google Scholar : PubMed/NCBI
18	Ourique F, Kviecinski MR, Felipe KB, Correia JF, Farias MS, Castro LS, Grinevicius VM, Valderrama J, Rios D, Benites J, et al: DNA damage and inhibition of akt pathway in mcf-7 cells and ehrlich tumor in mice treated with 1,4-naphthoquinones in combination with ascorbate. Oxid Med Cell Longev. 2015:4953052015. View Article : Google Scholar : PubMed/NCBI
19	Davis WJ, Lehmann PZ and Li W: Nuclear PI3K signaling in cell growth and tumorigenesis. Front Cell Dev Biol. 3:242015. View Article : Google Scholar : PubMed/NCBI
20	Liu Z, Zhu G, Getzenberg RH and Veltri RW: The upregulation of PI3K/Akt and MAP kinase pathways is associated with resistance of microtubule-targeting drugs in prostate cancer. J Cell Biochem. 116:1341–1349. 2015. View Article : Google Scholar : PubMed/NCBI
21	King SM, Quartuccio SM, Vanderhyden BC and Burdette JE: Early transformative changes in normal ovarian surface epithelium induced by oxidative stress require Akt upregulation, DNA damage and epithelial-stromal interaction. Carcinogenesis. 34:1125–1133. 2013. View Article : Google Scholar : PubMed/NCBI