Abstract: Objective To investigate the relationship between autophagy and metastasis of nasopharyngeal cancer (NPC) cell lines 5-8F and 6-10B after X-ray irradiation and the related mechanism. Methods Two substrains, 5-8F and 6-10B, of the NPC cell line SUNE1, with high and low metastatic potentials, respectively, were used in our study. After 4 Gy X-ray irradiation, 5-8F cells were treated with rapamycin (2.0 μmol/L) to induce autophagy and 6-10B cells were treated with LY294002(10 μmol/L) to inhibit autophagy. The autophagy and metastatic activity of NPC cells were determined using qRT-PCR, Western blot, Transwell assay, laser confocal microscopy, and transmission electron microscopy. Results 5-8F cells showed a lower level of autophagy than 6-10B cells after X-ray irradiation. Rapamycin increased the autophagy and inhibited the metastasis of 5-8F cells after irradiation, while LY294002 inhibited the autophagy and increased the metastasis of 6-10B cells. Conclusions NPC 5-8F cells, which have a high metastatic potential, have a lower level of autophagy than 6-10B cells, which have a low metastatic potential. Autophagic inhibition could increase the metastatic activity of NPC cells, while autophagic activation could reduce their metastatic activity. Mechanistic analysis indicates that the PI3K/AKT/mTOR pathway is involved in this process.
Mao Jianguo,Ma Rui,Zhao Lina et al. A preliminary study of the relationship between autophagy and metastasis of nasopharyngeal carcinoma cells after X-ray irradiation[J]. Chinese Journal of Radiation Oncology, 2017, 26(3): 324-328.
[1] Degenhardt K, Mathew R, Beaudoin B,et al. Autophagy promotes tumor cell survival and restricts necrosis,inflammation,and tumorigenesis[J].Cancer Cell,2006,10(1):51-64.DOI:10.1016/j.ccr.2006.06.001. [2] Choi AMK,Ryter SW,Levine B.Autophagy in human health and disease[J].New Engl J Med,2013,368(7):651-662.DOI:10.1056/NEJMra1205406. [3] Zhang J, Yang Z, Xie L,et al. Statins,autophagy and cancer metastasis[J].Int J Bioch Cell Biol,2013,45(3):745-752.DOI:10.1016/j.biocel.2012.11.001. [4] Shi Z, Li CY, Zhao S,et al. A systems biology analysis of autophagy in cancer therapy[J].Cancer Lett,2013,337(2):149-160.DOI:10.1016/j.canlet.2013.06.004. [5] Maes H, Kuchnio A, Peric A,et al. Tumor vessel normalization by chloroquine independent of autophagy[J].Cancer Cell,2014,26(2):190-206.DOI:10.1016/j.ccr.2014.06.025. [6] Lung HL, Bangarusamy DK, Xie D, et al. THY1 is a candidate tumour suppressor gene with decreased expression in metastatic nasopharyngeal carcinoma[J].Oncogene,2005,24(43):6525-6532.DOI:10.1038/sj.onc.1208812. [7] Liu SC, Jen YM, Jiang SS, et al. G (alpha)12-mediated pathway promotes invasiveness of nasopharyngeal carcinoma by modulating actin cytoskeleton reorganization[J].Cancer Res,2009,69(15):6122-6130.DOI:10.1158/0008-5472.CAN-08-3435. [8] Klionsky DJ.A human autophagy interaction network.[J].Autophagy, 2012, 8(4):439.DOI:10.4161/auto.19926. [9] Xie R, Fen Wang, Wallace L,et al. Autophagy enhanced by microtubule and mitochondrion-associated MAP1S suppresses genome instability and hepatocarcinogenesis[J].Cancer Res,2011,71(24):7537-7546.DOI:10.1158/0008-5472.CAN-11-2170. [10] Wu YT, Tan HL, Huang Q,et al. Activation of the PI3K-Akt-mTOR signaling pathway promotes necrotic cell death via suppression of autophagy[J].Autophagy,2009,5(6):824-834.DOI:10.4161/auto.9099. [11] Finn RS.Current and future treatment strategies for patients with advanced hepatocellular carcinoma:role of mTOR inhibition[J].Liver Cancer,2012,1(3-4):247-256.DOI:10.1159/000343839. [12] Lee J,Giordano S,Zhang J.Autophagy,mitochondria and oxidative stress:cross-talk and redox signalling[J].Bioch J,2012,441(2):523-540.DOI:10.1042/BJ20111451. [13] Kung CP, Budina A, Balaburski G,et al. Autophagy in tumor Suppression and cancer therapy[J].Cri Rev Eukary Gene Exp,2011,21(1):71-100.DOI:10.1615/critreveukargeneexpr.v21.i1.50.