Effect of melatonin on the expression of Th1/Th2/Th17 cytokines of gastric cancer in vitro and in vivo

CAI Rong ZHU Yu WANG Kai-fang ZHOU Rui-xiang LIU Hui

Acta Anatomica Sinica ›› 2019, Vol. 50 ›› Issue (4) : 471-476.

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Acta Anatomica Sinica ›› 2019, Vol. 50 ›› Issue (4) : 471-476. DOI: 10.16098/j.issn.0529-1356.2019.04.011
Cancer Biology

Effect of melatonin on the expression of Th1/Th2/Th17 cytokines of gastric cancer in vitro and in vivo

  • CAI Rong ZHU Yu WANG Kai-fang ZHOU Rui-xiang LIU Hui*
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Abstract

Objective To investigate the effect of melatonin(MLT) on the expression of type Th1/Th2/Th17 cytokines such as interferon(IFN)-γ, tumor necrosis factor(TNF), interleukin(IL)-2,IL-4,IL-6,IL-10,IL-17a and so on of gastric cancer in vitro and in vivo. Methods 1. Model of gastric cancer-bearing mice was established. Then 32 male 615 mice were all inoculated with murine foregastric carcinoma cells and randomly divided into 4 groups, and injected intraperitoneally with melatonin at doses of 0, 25, 50 and 100 mg/kg, and measureed long and short diameter of tumor, respectively. After a week of intervention, peripheral blood was taken and the tumor tissue was removed for weighing and measurement. 2. Murine foregastric carcinoma (MFC)cells were inoculated into a six-well cell culture plate and routinely cultured. After 24 hours of adherence, they were treated with melatonin at different concentrations of 0, 2, 4, 6, 8 and 10 mmol/L. After 24 hours again, the cells morpology were observed and the corresponding supernatants were collected. 3. The expressions of melatonin concentrations in peripheral blood serum was detected by enzyme -linked imm unosorbent assay (ELISA). The expressions of Th1/Th2/Th17 cytokines in peripheral blood serum and cell supernatants were detected by cytometric bead array (CBA) respectively. Results 1. Tumor-bearing mice models were successfully established. Compared with the negative control group, the melatonin concentration in peripheral blood serum of the middle and high dose MLT group which increased significantly, and the tumor volume significantly decreased. Compared with the negative control group, the concentration of IL-10 in the middle dose group increased significantly. And the concentration of IFN-γ, IL-2 and IL-10 in the high dose group increased significantly too. 2. Compared with the 0 mmol/L MLT group, the concentrations of IFN-γ in the 6 and 10 mmol/L MLT group were significantly decreased; the concentrations of IL-6 in the 4, 6, 8 and 10 mmol/L MLT group were significantly decreased, and the concentration of IL-10 in 6 mmol/L MLT group was significantly increased. All the difference were statistically significant (P<0.05). Conclusion Melatonin inhibits the proliferation of murine foregastric carcinoma cell MFC both in vitro and in vivo, and may enhance tumor immunity by adjust the expression of IFN-γ, IL-2, IL-6 and IL-10 cytokines of type Th1/Th2/Th17 cells.

Key words

Melatonin / Gastric cancer / Th1/Th2/Th17 cytokines / Cytometric bead array / Mouse

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CAI Rong ZHU Yu WANG Kai-fang ZHOU Rui-xiang LIU Hui. Effect of melatonin on the expression of Th1/Th2/Th17 cytokines of gastric cancer in vitro and in vivo[J]. Acta Anatomica Sinica. 2019, 50(4): 471-476 https://doi.org/10.16098/j.issn.0529-1356.2019.04.011

References

 [1] Haidong W, Mohsen N, Christine A, et al. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015[J]. Lancet, 2016, 388(10053): 1459-1544.
 [2] Chen WQ, Zheng RS, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132.
 [3] Jemal A, Bray F, Center MM, et al. Global cancer statistics[J]. CA Cancer J Clin, 2011, 61(2): 134.
 [4] Carbajo-Pescador S, Ordonez R, Benet M, et al. Inhibition of VEGF expression through blockade of Hif1alpha and STAT3 signalling mediates the anti-angiogenic effect of melatonin in HepG2 liver cancer cells[J]. Br J Cancer, 2013, 109(1): 83-91. 
 [5] Goradel NH, Asghari MH, Moloudizargari M, et al. Melatonin as an angiogenesis inhibitor to combat cancer: mechanistic evidence[J]. Toxicol Appl Pharmacol, 2017,335(21):56-63. 
 [6] Radogna F, Diederich M, Ghibelli L. Melatonin: a pleiotropic molecule regulating inflammol/Lation[J]. Biochem Pharmacol, 2010, 80(12): 1844-1852.
 [7] Muc-Wierzgon M, Nowakowska ZE, Zubelewicz B, et al. Circadian fluctuations of melatonin, tumor necrosis factor-alpha and its soluble receptors in the Circulation of patients with advanced gastrointestinal cancer[J].J Exp Clin Cancer Res,2003, 22(2): 171-178.
 [8] Cardinali DP,Cano P,Jiménez-Ortega V, et al. Melatonin and the metabolic syndrome: physiopathologic and therapeutical implications[J]. Neuroendocrinology, 2011,93(3):133-142.
 [9] Zou ZW,Liu T,Li Y, et al. Melatonin suppresses thyroid cancer growth and overcomes radioresistance via inhibition of p65 phosphorylation and induction of ROS[J]. Redox Biol,2018,16(6):226-236.
 [10] Kubatka P, Zubor P, Busselberg D, et al. Melatonin and breast cancer: evidences from preclinical and human studies[J]. Crit Rev Oncol Hematol,2018,122 (2):133-143.
 [11] Shen CJ, Chang CC, Chen YT,et al. Melatonin suppresses the growth of ovarian cancer cell lines (OVCAR-429 and PA-1) and potentiates the effect of G1 arrest by targeting CDKs[J]. Int J Mol Sci, 2016,17(2): 176-187.
 [12] Asghari MH, Moloudizargari M, Ghobadi E, et al. Melatonin as a multifunctional anti-cancer molecule: implications in gastric cancer[J]. Life Sci, 2017,185(31):38-45. 
 [13] Liu H, Jiang JH, Xu L, et al. Effect of melatonin on proliferation inhibition and apoptosis induction in the murine foregastric carcinoma cell in vivo and in vitro[J]. Acta Anatomica Sinica, 2011,42(6):792-797. (in Chinese)
刘卉,蒋继浩,徐丽,等. 褪黑素体内外对小鼠前胃癌细胞的增殖抑制与凋亡诱导作用[J].解剖学报,2011,42(6):792-797.
 [14] Zhou MX, Tu JR. Correlation analysis of IL-2, IL-10 and their sensitivity to chemoradiation in patients with nasopharyngeal carcinoma[J]. Journal of Practical Cancer, 2017, 32(4): 598-602. (in Chinese)
周美秀,涂建仁. 鼻咽癌外周血IL-2,IL-10水平与其放化疗敏感性的相关性分析[J]. 实用癌症杂志, 2017, 32(4): 598-602.
 [15] Yi X,Tang AZh, Qin Y. Detection of IL -10 and IL -12 in the patients with nasopharyngeal carcinoma[J]. Chinese Journal of Moder n Medicine, 2009, 11(8): 46-48. (in Chinese)
易翔,唐安洲,覃颖. 鼻咽癌中白细胞介素-10,白细胞介素-12检测及其意义[J]. 中国现代医药杂志, 2009, 11(8): 46-48.
 [16] Khaghanzadeh N, Samiei A, Ramezani M, et al. Umbelliprenin induced production of INF-γ and TNF-α, and reduced IL-10, IL-4, Foxp3 and TGF-β in a mouse model of lung cancer[J]. Immunopharmacol Immunotoxicol, 2014, 36(1): 25-32.
 [17] Abiko K, Matsumura N, Hamanishi J, et al. INF-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer[J]. Br J Cancer, 2015, 112(9): 1501-1509.  
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