Inhibitory effect of melatonin on murine foregastric carcinoma cells via membrane receptors MT2

doi:10.3969/j.issn.0529-1356.2014.03.009

Abstract

Abstract:

Objective To investigate the inhibitory effect of melatonin on the proliferation activity of murine foregastic carcinomac (MFC) cells via melatonin membrane receptors MT2 and its relationship with the signaling pathways of mitogen-activated protein kinases (MAPKs), phosphatidylinositol 3-kinase(PI3K)-Akt. Methods Using siRNA technology to silence MT2 expression, we examined the ability of melatonin to inhibit the proliferation activity of MFC cells and its influence on the phosphorylation of ERK1/2 and Akt. Results We found two interesting effects of SiRNA-mediated silencing of MT2 expression. Firstly, it significantly antagonized the inhibitory effect of melatonin on the proliferation activity of MFC cells. Secondly, it partially blocked the inhibitory effect of melatonin on the phosphorylation of ERK1/2 and Akt. Conclusion Our results suggest that melatonin can inhibit the phosphorylation of ERK1/2 and Akt via MT2 receptors, thereby inhibiting the proliferation of gastric cancer cells.

Key words: Melatonin, Murine foregastic carcinoma cell, Melatonin membrane receptor MT2, Akt, ERK1/2, Real-time PCR, Mouse

XU Li JIN Qing-dong GONG Xi LIU Hui ZHOU Rui-xiang*. Inhibitory effect of melatonin on murine foregastric carcinoma cells via membrane receptors MT2[J]. AAS, 2014, 45(3): 344-349.

References

［1］Crew KD, Neugut AI. Epidemiology of gastric cancer［J］. World J Gastroenterol, 2006, 12（3）: 354-362.
［2］Sánchez-Hidalgo M, Lee M, de la Lastra CA, et al. Melatonin inhibits cell proliferation and induces caspase activation and apoptosis in human malignant lymphoid cell lines ［J］. J Pineal Res, 2012, 53(4): 366-373.
［3］Tam CW, Shiu SY. Functional interplay between melatonin receptormediated antiproliferative signaling and androgen receptorsignaling in human prostate epithelial cells: potential implications for therapeutic strategies against prostate cancer［J］. J Pineal Res, 2011, 51(3):297-312. 
［4］Konturek PC, Konturek SJ, Burnat G, et al. Dynamic physiological and molecular changes in gastric ulcer healing achieved by melatonin and its precursor L-tryptophan in rats［J］. J Pineal Res, 2008, 45（2）:180-190.
［5］Blask DE, Sauer LA, Dauchy RT. Melatonin as a chronobiotic/anticancer agent: cellular, biochemical, and molecular mechanisms of action and their implications for circadian-based cancer therapy［J］. Curr Top Med Chem, 2002, 2（2）: 113-132.
［6］Xu L, Liu H, Zhang H, et al. Growth-inhibitory activity of melatoninon murine foregastric carcinom a cells in vitro and the underlying molecular mechanism［J］. Anat Rec, 2013, 296:914-920.
［7］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.
［8］Liu H, Xu L, Wei JE, et al. Role of CD4+ CD25+ regulatory T cells in melatonin-mediated inhibition of murine gastric cancer cell growth in vivo and in vitro［J］. Anat Rec, 2011, 294(5):781-788.
［9］Cutando A, Aneiros-Fernández J, Aneiros-Cachaza J, et al. Melatonin and cancer: current knowledge and its application to oral cavity tumours［J］. J Oral Pathol Med, 2011, 40（8）:593-597.
［10］Kobayashi Y, Itoh MT, Kondo H, et al. Melatonin binding sites in estrogen receptor-positive cells derived from human endometrial cancer［J］. J Pineal Res, 2003, 35（2）: 71-74.
［11］Kanishi Y, Kobayashi Y, Noda S, et al. Differential growth inhibitory effect of melatonin on two endometrial cancer cell lines［J］. J Pineal Res, 2000, 28（4）: 227-233.
［12］Winczyk K, Pawlikowski M, Lawnicka H, et al. Effects of melatonin and melatonin receptors ligand N-［(4-methoxy-1H-indol-2-yl)methyl］ propanamide on murine Colon 38 cancer growth in vitro and in vivo［J］. Neuro Endocrinol Lett, 2002, 23（Suppl 1）: 50-54.
［13］Souza AV, Visconti MA, Castrucci AM. Melatonin biological activity and binding sites in human melanoma cells［J］. J Pineal Res, 2003, 34（4）: 242-248. 
［14］Motilva V, Cabeza J, Alarcon de la Lastra C. New issues about melatonin and its effects on the digestive system［J］. Curr Pharm Des, 2001, 7（10）: 909-931.
［15］Kim JH, Jeong SJ, Kim B, et al. Melatonin synergistically enhances cisplatin-induced apoptosis via the dephosphorylation of ERK/p90 ribosomal S6 kinase/heat shock protein 27 in SK-OV-3 cells［J］. J Pineal Res, 2012, 52（2）: 244-252. 
［16］Nicholson KM, Anderson NG. The protein kinase B/Akt signalling pathway in human malignancy［J］.Cell Signal, 2002, 14（5）: 381-395.
［17］Lee HY, Crawley S, Hokari R, et al. Bile acid regulates MUC2 transcription in colon cancer cells via positive EGFR/PKC/Ras/ERK/CREB, PI3K/Akt/IkappaB/NF-kappaB and p38/MSK1/CREB pathways and negative JNK/c-Jun/AP-1 pathway［J］. Int J Oncol, 2010, 36(4):941-953.
［18］Cui P, Yu M, Luo Z, et al. Intracellular signaling pathways involved in cell growth inhibition of human umbilical vein endothelial cells bymelatonin［J］. J Pineal Res, 2008, 44(1):107-114.
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