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Article

Melatonin induces the apoptosis and inhibits the proliferation of human gastric cancer cells via blockade of the AKT/MDM2 pathway

  • Authors:
    • Jun Song
    • Sai-Jun Ma
    • Jian-Hua Luo
    • Hui Zhang
    • Ri-Xiong Wang
    • Hui Liu
    • Li Li
    • Zhi-Guang Zhang
    • Rui-Xiang Zhou
  • View Affiliations / Copyright

    Affiliations: Department of Cell Biology and Genetics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian 350108, P.R. China, Clinical Laboratory, Second Inpatient Department, Fuzhou General Hospital, Fuzhou, Fujian 350108, P.R. China, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian 350108, P.R. China, Fujian Center for Safety Evaluation of New Drugs, Fujian Medical University, Fuzhou, Fujian 350108, P.R. China, Department of Chemotherapy, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350108, P.R. China, Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian 350108, P.R. China
  • Pages: 1975-1983
    |
    Published online on: February 26, 2018
       https://doi.org/10.3892/or.2018.6282
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Abstract

Globally, gastric cancer (GC) is one of the most common types of cancer and the third leading cause of cancer‑related death. In China, gastric and liver cancers have the highest mortality rates. Melatonin, also known as N-acetyl‑5-methoxytryptamine, is a hormone that is produced by the pineal gland in animals and regulates sleep and wakefulness. Melatonin has been shown to inhibit various carcinomas, including GC. There are many different hypotheses to explain the anticancer effects of melatonin, including stimulation of apoptosis, inhibition of cell growth, regulation of anticancer immunity, induction of free-radical scavenging, and the competitive inhibition of estrogen. However, the underlying mechanism by which these effects are elicited remains elusive. The aim of the present study was to investigate the effects of melatonin on human GC cells and determine the underlying molecular mechanism. We treated SGC-7901 GC cells with melatonin and analyzed the resulting protein changes using protein chip technology. Several proteins related to cell apoptosis and proliferation were identified and further tested in SGC-7901 GC cells. We found that melatonin induced cell cycle arrest and the downregulation of CDC25A, phospho-CDC25A (at Ser75), p21 (p21Cip1/p21Waf1) and phospho-p21 (at Thr145). Melatonin also induced upregulation of Bax, downregulation of Bcl-xL, an increase in cleaved caspase-9 level and activation of caspase-3, which confirmed the involvement of the mitochondria in melatonin‑induced apoptosis. Upstream regulators of the above proteins, MDM2, phospho-MDM2 (at Ser166) and AKT, phospho-AKT (at Thr308) were all attenuated by melatonin, which led to an increase in p53. The present study demonstrated that the oncostatic effects of melatonin on SGC-7901 GC cells are mediated via the blockade of the AKT/MDM2 intracellular pathway.
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View References

1 

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

2 

World Health Organization, . World Cancer Report 2014. World Health Organization; Geneva: 2014

3 

Voiculescu SE, Zygouropoulos N, Zahiu CD and Zagrean AM: Role of melatonin in embryo fetal development. J Med Life. 7:488–492. 2014.PubMed/NCBI

4 

Karaaslan C and Suzen S: Antioxidant properties of melatonin and its potential action in diseases. Curr Top Med Chem. 15:894–903. 2015. View Article : Google Scholar : PubMed/NCBI

5 

Acuña-Castroviejo D, Escames G, Venegas C, Díaz-Casado ME, Lima-Cabello E, López LC, Rosales-Corral S, Tan DX and Reiter RJ: Extrapineal melatonin: Sources, regulation, and potential functions. Cell Mol Life Sci. 71:2997–3025. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Bubenik GA: Thirty four years since the discovery of gastrointestinal melatonin. J Physiol Pharmacol. 59 Suppl 2:33–51. 2008.PubMed/NCBI

7 

Bubenik GA: Gastrointestinal melatonin: Localization, function, and clinical relevance. Dig Dis Sci. 47:2336–2348. 2002. View Article : Google Scholar : PubMed/NCBI

8 

Kolli VK, Kanakasabapathy I, Faith M, Ramamoorthy H, Isaac B, Natarajan K and Abraham P: A preclinical study on the protective effect of melatonin against methotrexate-induced small intestinal damage: Effect mediated by attenuation of nitrosative stress, protein tyrosine nitration, and PARP activation. Cancer Chemother Pharmacol. 71:1209–1218. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Lissoni P, Barni S, Crispino S, Tancini G and Fraschini F: Endocrine and immune effects of melatonin therapy in metastatic cancer patients. Eur J Cancer Clin Oncol. 25:789–795. 1989. View Article : Google Scholar : PubMed/NCBI

10 

Zhang S, Qi Y, Zhang H, He W, Zhou Q, Gui S and Wang Y: Melatonin inhibits cell growth and migration, but promotes apoptosis in gastric cancer cell line, SGC7901. Biotech Histochem. 88:281–289. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Wang RX, Liu H, Xu L, Zhang H and Zhou RX: Involvement of nuclear receptor RZR/RORγ in melatonin-induced HIF-1α inactivation in SGC-7901 human gastric cancer cells. Oncol Rep. 34:2541–2546. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Wang RX, Liu H, Xu L, Zhang H and Zhou RX: Melatonin downregulates nuclear receptor RZR/RORγ expression causing growth-inhibitory and anti-angiogenesis activity in human gastric cancer cells in vitro and in vivo. Oncol Lett. 12:897–903. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Li W, Fan M, Chen Y, Zhao Q, Song C, Yan Y, Jin Y, Huang Z, Lin C and Wu J: Melatonin induces cell apoptosis in AGS cells through the activation of JNK and P38 MAPK and the suppression of nuclear factor-kappa B: A novel therapeutic implication for gastric cancer. Cell Physiol Biochem. 37:2323–2338. 2015. View Article : Google Scholar : PubMed/NCBI

14 

Carbajo-Pescador S, Ordoñez R, Benet M, Jover R, García-Palomo A, Mauriz JL and González-Gallego J: Inhibition of VEGF expression through blockade of Hif1α and STAT3 signalling mediates the anti-angiogenic effect of melatonin in HepG2 liver cancer cells. Br J Cancer. 109:83–91. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Fan L, Sun G, Ma T, Zhong F and Wei W: Melatonin overcomes apoptosis resistance in human hepatocellular carcinoma by targeting survivin and XIAP. J Pineal Res. 55:174–183. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Fan L, Sun G, Ma T, Zhong F, Lei Y, Li X and Wei W: Melatonin reverses tunicamycin-induced endoplasmic reticulum stress in human hepatocellular carcinoma cells and improves cytotoxic response to doxorubicin by increasing CHOP and decreasing survivin. J Pineal Res. 55:184–194. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Ordoñez R, Carbajo-Pescador S, Prieto-Dominguez N, García-Palomo A, González-Gallego J and Mauriz JL: Inhibition of matrix metalloproteinase-9 and nuclear factor kappa B contribute to melatonin prevention of motility and invasiveness in HepG2 liver cancer cells. J Pineal Res. 56:20–30. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Alvarez-García V, González A, Alonso-González C, Martínez-Campa C and Cos S: Regulation of vascular endothelial growth factor by melatonin in human breast cancer cells. J Pineal Res. 54:373–380. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Blask DE, Dauchy RT, Dauchy EM, Mao L, Hill SM, Greene MW, Belancio VP, Sauer LA and Davidson L: Light exposure at night disrupts host/cancer circadian regulatory dynamics: Impact on the Warburg effect, lipid signaling and tumor growth prevention. PLoS One. 9:e1027762014.doi: 10.1371/journal.pone.0102776. View Article : Google Scholar : PubMed/NCBI

20 

Cos S, Alvarez-García V, González A, Alonso-González C and Martínez-Campa C: Melatonin modulation of crosstalk among malignant epithelial, endothelial and adipose cells in breast cancer (Review). Oncol Lett. 8:487–492. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Proietti S, Cucina A, Dobrowolny G, D'Anselmi F, Dinicola S, Masiello MG, Pasqualato A, Palombo A, Morini V, Reiter RJ, et al: Melatonin down-regulates MDM2 gene expression and enhances p53 acetylation in MCF-7 cells. J Pineal Res. 57:120–129. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Cutando A, López-Valverde A, DE Vicente J, Gimenez JL, Carcía IA and DE Diego RG: Action of melatonin on squamous cell carcinoma and other tumors of the oral cavity (Review). Oncol Lett. 7:923–926. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Goncalves NN, Rodrigues RV, Jardim-Perassi BV, Moschetta MG, Lopes JR, Colombo J and Zuccari DA: Molecular markers of angiogenesis and metastasis in lines of oral carcinoma after treatment with melatonin. Anticancer Agents Med Chem. 14:1302–1311. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Rodriguez-Garcia A, Mayo JC, Hevia D, Quiros-Gonzalez I, Navarro M and Sainz RM: Phenotypic changes caused by melatonin increased sensitivity of prostate cancer cells to cytokine-induced apoptosis. J Pineal Res. 54:33–45. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Shiu SY, Leung WY, Tam CW, Liu VW and Yao KM: Melatonin MT1 receptor-induced transcriptional up-regulation of p27(Kip1) in prostate cancer antiproliferation is mediated via inhibition of constitutively active nuclear factor kappa B (NF-κB): Potential implications on prostate cancer chemoprevention and therapy. J Pineal Res. 54:69–79. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Paroni R, Terraneo L, Bonomini F, Finati E, Virgili E, Bianciardi P, Favero G, Fraschini F, Reiter RJ, Rezzani R, et al: Antitumour activity of melatonin in a mouse model of human prostate cancer: Relationship with hypoxia signalling. J Pineal Res. 57:43–52. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Liu H, Xu L, Wei JE, Xie MR, Wang SE and Zhou RX: Role of CD4+ CD25+ regulatory T cells in melatonin-mediated inhibition of murine gastric cancer cell growth in vivo and in vitro. Anat Rec (Hoboken). 294:781–788. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Xu L, Jin QD, Gong X, Liu H and Zhou RX: Anti-gastric cancer effect of melatonin and Bcl-2, Bax, p21 and p53 expression changes. Sheng Li Xue Bao. 66:723–729. 2014.(In Chinese). PubMed/NCBI

29 

Fakharzadeh SS, Trusko SP and George DL: Tumorigenic potential associated with enhanced expression of a gene that is amplified in a mouse tumor cell line. EMBO J. 10:1565–1569. 1991.PubMed/NCBI

30 

Zak K, Pecak A, Rys B, Wladyka B, Dömling A, Weber L, Holak TA and Dubin G: Mdm2 and MdmX inhibitors for the treatment of cancer: A patent review (2011-present). Expert Opin Ther Pat. 23:425–448. 2013. View Article : Google Scholar : PubMed/NCBI

31 

Shaikh MF, Morano WF, Lee J, Gleeson E, Babcock BD, Michl J, Sarafraz-Yazdi E, Pincus MR and Bowne WB: Emerging role of MDM2 as target for anti-cancer therapy: A review. Ann Clin Lab Sci. 46:627–634. 2016.PubMed/NCBI

32 

He J, Zhu G, Gao L, Chen P, Long Y, Liao S, Yi H, Yi W, Pei Z, Wu M, et al: Fra-1 is upregulated in gastric cancer tissues and affects the PI3K/Akt and p53 signaling pathway in gastric cancer. Int J Oncol. 47:1725–1734. 2015. View Article : Google Scholar : PubMed/NCBI

33 

Eischen CM and Lozano G: p53 and MDM2: Antagonists or partners in crime? Cancer Cell. 15:161–162. 2009. View Article : Google Scholar : PubMed/NCBI

34 

Nakajima N, Ito Y, Yokoyama K, Uno A, Kinukawa N, Nemoto N and Moriyama M: The expression of murine double minute 2 (MDM2) on Helicobacter pylori-infected intestinal metaplasia and gastric cancer. J Clin Biochem Nutr. 44:196–202. 2009. View Article : Google Scholar : PubMed/NCBI

35 

Günther T, Schneider-Stock R, Häckel C, Kasper HU, Pross M, Hackelsberger A, Lippert H and Roessner A: Mdm2 gene amplification in gastric cancer correlation with expression of Mdm2 protein and p53 alterations. Mod Pathol. 13:621–626. 2000. View Article : Google Scholar : PubMed/NCBI

36 

Sun LP, Jiang NJ, Fu W, Xue YX and Zhao YS: Relationship between gastric cancer and gene amplification of p14 and mdm2. Ai Zheng. 23:36–39. 2004.(In Chinese). PubMed/NCBI

37 

Manfredi JJ: The Mdm2-p53 relationship evolves: Mdm2 swings both ways as an oncogene and a tumor suppressor. Genes Dev. 24:1580–1589. 2010. View Article : Google Scholar : PubMed/NCBI

38 

Carter S, Bischof O, Dejean A and Vousden KH: C-terminal modifications regulate MDM2 dissociation and nuclear export of p53. Nat Cell Biol. 9:428–435. 2007. View Article : Google Scholar : PubMed/NCBI

39 

Lohrum MA, Woods DB, Ludwig RL, Bálint E and Vousden KH: C-terminal ubiquitination of p53 contributes to nuclear export. Mol Cell Biol. 21:8521–8532. 2001. View Article : Google Scholar : PubMed/NCBI

40 

Zauberman A, Barak Y, Ragimov N, Levy N and Oren M: Sequence-specific DNA binding by p53: Identification of target sites and lack of binding to p53 - MDM2 complexes. EMBO J. 12:2799–2808. 1993.PubMed/NCBI

41 

Poyurovsky MV, Katz C, Laptenko O, Beckerman R, Lokshin M, Ahn J, Byeon IJ, Gabizon R, Mattia M, Zupnick A, et al: The C terminus of p53 binds the N-terminal domain of MDM2. Nat Struct Mol Biol. 17:982–989. 2010. View Article : Google Scholar : PubMed/NCBI

42 

Cross B, Chen L, Cheng Q, Li B, Yuan ZM and Chen J: Inhibition of p53 DNA binding function by the MDM2 protein acidic domain. J Biol Chem. 286:16018–16029. 2011. View Article : Google Scholar : PubMed/NCBI

43 

Biderman L, Poyurovsky MV, Assia Y, Manley JL and Prives C: MdmX is required for p53 interaction with and full induction of the Mdm2 promoter after cellular stress. Mol Cell Biol. 32:1214–1225. 2012. View Article : Google Scholar : PubMed/NCBI

44 

Bond GL, Hu W, Bond EE, Robins H, Lutzker SG, Arva NC, Bargonetti J, Bartel F, Taubert H, Wuerl P, et al: A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell. 119:591–602. 2004. View Article : Google Scholar : PubMed/NCBI

45 

Bond GL, Hu W and Levine A: A single nucleotide polymorphism in the MDM2 gene: From a molecular and cellular explanation to clinical effect. Cancer Res. 65:5481–5484. 2005. View Article : Google Scholar : PubMed/NCBI

46 

Ofir-Rosenfeld Y, Boggs K, Michael D, Kastan MB and Oren M: Mdm2 regulates p53 mRNA translation through inhibitory interactions with ribosomal protein L26. Mol Cell. 32:180–189. 2008. View Article : Google Scholar : PubMed/NCBI

47 

Mayo LD and Donner DB: A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus. Proc Natl Acad Sci USA. 98:pp. 11598–11603. 2001; View Article : Google Scholar : PubMed/NCBI

48 

Zhou BP, Liao Y, Xia W, Zou Y, Spohn B and Hung MC: HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation. Nat Cell Biol. 3:973–982, 2001. Nat Cell Biol 3: 973–982. 2001. View Article : Google Scholar : PubMed/NCBI

49 

Gottlieb TM, Leal JF, Seger R, Taya Y and Oren M: Cross-talk between Akt, p53 and Mdm2: Possible implications for the regulation of apoptosis. Oncogene. 21:1299–1303. 2002. View Article : Google Scholar : PubMed/NCBI

50 

Jones SN, Hancock AR, Vogel H, Donehower LA and Bradley A: Overexpression of Mdm2 in mice reveals a p53-independent role for Mdm2 in tumorigenesis. Proc Natl Acad Sci USA. 95:pp. 15608–15612. 1998; View Article : Google Scholar : PubMed/NCBI

51 

McDonnell TJ, Montes de Oca Luna R, Cho S, Amelse LL, Chavez-Reyes A and Lozano G: Loss of one but not two mdm2 null alleles alters the tumour spectrum in p53 null mice. J Pathol. 188:322–328. 1999. View Article : Google Scholar : PubMed/NCBI

52 

Dobbelstein M, Wienzek S, König C and Roth J: Inactivation of the p53-homologue p73 by the mdm2-oncoprotein. Oncogene. 18:2101–2106. 1999. View Article : Google Scholar : PubMed/NCBI

53 

Zeng X, Chen L, Jost CA, Maya R, Keller D, Wang X, Kaelin WG Jr, Oren M, Chen J and Lu H: MDM2 suppresses p73 function without promoting p73 degradation. Mol Cell Biol. 19:3257–3266. 1999. View Article : Google Scholar : PubMed/NCBI

54 

Gu J, Nie L, Kawai H and Yuan ZM: Subcellular distribution of p53 and p73 are differentially regulated by MDM2. Cancer Res. 61:6703–6707. 2001.PubMed/NCBI

55 

Watson IR, Blanch A, Lin DC, Ohh M and Irwin MS: Mdm2-mediated NEDD8 modification of TAp73 regulates its transactivation function. J Biol Chem. 281:34096–34103. 2006. View Article : Google Scholar : PubMed/NCBI

56 

Cheney MD, McKenzie PP, Volk EL, Fan L and Harris LC: MDM2 displays differential activities dependent upon the activation status of NFkappaB. Cancer Biol Ther. 7:38–44. 2008. View Article : Google Scholar : PubMed/NCBI

57 

Sun P, Dong P, Dai K, Hannon GJ and Beach D: p53-independent role of MDM2 in TGF-beta1 resistance. Science. 282:2270–2272. 1998. View Article : Google Scholar : PubMed/NCBI

58 

Yam CH, Siu WY, Arooz T, Chiu CH, Lau A, Wang XQ and Poon RY: MDM2 and MDMX inhibit the transcriptional activity of ectopically expressed SMAD proteins. Cancer Res. 59:5075–5078. 1999.PubMed/NCBI

59 

Xiao ZX, Chen J, Levine AJ, Modjtahedi N, Xing J, Sellers WR and Livingston DM: Interaction between the retinoblastoma protein and the oncoprotein MDM2. Nature. 375:694–698. 1995. View Article : Google Scholar : PubMed/NCBI

60 

Sdek P, Ying H, Zheng H, Margulis A, Tang X, Tian K and Xiao ZX: The central acidic domain of MDM2 is critical in inhibition of retinoblastoma-mediated suppression of E2F and cell growth. J Biol Chem. 279:53317–53322. 2004. View Article : Google Scholar : PubMed/NCBI

61 

Zhou S, Gu L, He J, Zhang H and Zhou M: MDM2 regulates vascular endothelial growth factor mRNA stabilization in hypoxia. Mol Cell Biol. 31:4928–4937. 2011. View Article : Google Scholar : PubMed/NCBI

62 

Thut CJ, Goodrich JA and Tjian R: Repression of p53-mediated transcription by MDM2: A dual mechanism. Genes Dev. 11:1974–1986. 1997. View Article : Google Scholar : PubMed/NCBI

63 

Minsky N and Oren M: The RING domain of Mdm2 mediates histone ubiquitylation and transcriptional repression. Mol Cell. 16:631–639. 2004. View Article : Google Scholar : PubMed/NCBI

64 

Ji W, Ma J, Zhang H, Zhong H, Li L, Ding N, Jiao J and Gao Z: Role of p53β in the inhibition of proliferation of gastric cancer cells expressing wild-type or mutated p53. Mol Med Rep. 12:691–695. 2015. View Article : Google Scholar : PubMed/NCBI

65 

Hoffmann I, Draetta G and Karsenti E: Activation of the phosphatase activity of human cdc25A by a cdk2-cyclin E dependent phosphorylation at the G1/S transition. EMBO J. 13:4302–4310. 1994.PubMed/NCBI

66 

Zou X, Tsutsui T, Ray D, Blomquist JF, Ichijo H, Ucker DS and Kiyokawa H: The cell cycle-regulatory CDC25A phosphatase inhibits apoptosis signal-regulating kinase 1. Mol Cell Biol. 21:4818–4828. 2001. View Article : Google Scholar : PubMed/NCBI

67 

Goloudina A, Yamaguchi H, Chervyakova DB, Appella E, Fornace AJ Jr and Bulavin DV: Regulation of human Cdc25A stability by Serine 75 phosphorylation is not sufficient to activate a S phase checkpoint. Cell Cycle. 2:473–478. 2003. View Article : Google Scholar : PubMed/NCBI

68 

Boutros R, Lobjois V and Ducommun B: CDC25 phosphatases in cancer cells: Key players? Good targets? Nat Rev Cancer. 7:495–507. 2007. View Article : Google Scholar : PubMed/NCBI

69 

Cheng M, Olivier P, Diehl JA, Fero M, Roussel MF, Roberts JM and Sherr CJ: The p21(Cip1) and p27(Kip1) CDK ‘inhibitors’ are essential activators of cyclin D-dependent kinases in murine fibroblasts. EMBO J. 18:1571–1583. 1999. View Article : Google Scholar : PubMed/NCBI

70 

Martín V, Herrera F, García-Santos G, Antolín I, Rodriguez-Blanco J, Medina M and Rodriguez C: Involvement of protein kinase C in melatonin's oncostatic effect in C6 glioma cells. J Pineal Res. 43:

71 

Rother K, Kirschner R, Sänger K, Böhlig L, Mössner J and Engeland K: p53 downregulates expression of the G1/S cell cycle phosphatase Cdc25A. Oncogene. 26:1949–1953. 2007. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Song J, Ma S, Luo J, Zhang H, Wang R, Liu H, Li L, Zhang Z and Zhou R: Melatonin induces the apoptosis and inhibits the proliferation of human gastric cancer cells via blockade of the AKT/MDM2 pathway. Oncol Rep 39: 1975-1983, 2018.
APA
Song, J., Ma, S., Luo, J., Zhang, H., Wang, R., Liu, H. ... Zhou, R. (2018). Melatonin induces the apoptosis and inhibits the proliferation of human gastric cancer cells via blockade of the AKT/MDM2 pathway. Oncology Reports, 39, 1975-1983. https://doi.org/10.3892/or.2018.6282
MLA
Song, J., Ma, S., Luo, J., Zhang, H., Wang, R., Liu, H., Li, L., Zhang, Z., Zhou, R."Melatonin induces the apoptosis and inhibits the proliferation of human gastric cancer cells via blockade of the AKT/MDM2 pathway". Oncology Reports 39.4 (2018): 1975-1983.
Chicago
Song, J., Ma, S., Luo, J., Zhang, H., Wang, R., Liu, H., Li, L., Zhang, Z., Zhou, R."Melatonin induces the apoptosis and inhibits the proliferation of human gastric cancer cells via blockade of the AKT/MDM2 pathway". Oncology Reports 39, no. 4 (2018): 1975-1983. https://doi.org/10.3892/or.2018.6282
Copy and paste a formatted citation
x
Spandidos Publications style
Song J, Ma S, Luo J, Zhang H, Wang R, Liu H, Li L, Zhang Z and Zhou R: Melatonin induces the apoptosis and inhibits the proliferation of human gastric cancer cells via blockade of the AKT/MDM2 pathway. Oncol Rep 39: 1975-1983, 2018.
APA
Song, J., Ma, S., Luo, J., Zhang, H., Wang, R., Liu, H. ... Zhou, R. (2018). Melatonin induces the apoptosis and inhibits the proliferation of human gastric cancer cells via blockade of the AKT/MDM2 pathway. Oncology Reports, 39, 1975-1983. https://doi.org/10.3892/or.2018.6282
MLA
Song, J., Ma, S., Luo, J., Zhang, H., Wang, R., Liu, H., Li, L., Zhang, Z., Zhou, R."Melatonin induces the apoptosis and inhibits the proliferation of human gastric cancer cells via blockade of the AKT/MDM2 pathway". Oncology Reports 39.4 (2018): 1975-1983.
Chicago
Song, J., Ma, S., Luo, J., Zhang, H., Wang, R., Liu, H., Li, L., Zhang, Z., Zhou, R."Melatonin induces the apoptosis and inhibits the proliferation of human gastric cancer cells via blockade of the AKT/MDM2 pathway". Oncology Reports 39, no. 4 (2018): 1975-1983. https://doi.org/10.3892/or.2018.6282
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