褪黑素抑制胃癌细胞系SGC-7901的迁移和侵袭

徐丽; 金清东; 陈秀娇; 陈超; 郑伟男; 周瑞祥

doi:10.16098/j.issn.0529-1356.2021.05.012

PDF(9163 KB)

解剖学报 ›› 2021, Vol. 52 ›› Issue (5) : 751-758. DOI: 10.16098/j.issn.0529-1356.2021.05.012

肿瘤生物学

褪黑素抑制胃癌细胞系SGC-7901的迁移和侵袭

徐丽^1*金清东² 陈秀娇¹陈超¹ 郑伟男¹ 周瑞祥^3*

作者信息 +

Melatonin inhibiting the migration and invasion of gastric cancer cell line SGC-7901#br#

XU Li¹* JIN Qing-dong² CHEN Xiu-jiao¹ CHEN Chao¹ ZHENG Wei-nan¹ ZHOU Rui-xiang^3*#br#

Author information +

文章历史 +

摘要

目的探讨褪黑素(MLT)对胃癌细胞迁移和侵袭的抑制作用及其分子机制。方法不同浓度(0.1、1、2 和4 mmol/L)的褪黑素干预人胃癌SGC-7901 细胞 24 h，应用划痕实验、Transwell小室法检测胃癌细胞迁移和侵袭能力的改变；ELISA试剂盒检测培养液上清中基质金属蛋白酶（MMP）-2、MMP-9的表达，Real-time PCR检测胃癌细胞MMP-2、MMP-9、细胞间黏附分子1(ICAM-1）和CD44基因表达；免疫印迹法检测ICAM-1、CD44、p-P38、P38和磷酸化丝裂原活化蛋白激酶激酶（p-MKK）3/6蛋白表达。结果褪黑素抑制胃癌细胞的迁移和侵袭，并呈剂量依赖性。与空白对照组比较，褪黑素降低胃癌细胞基质金属蛋白酶（MMP)-2、MMP-9和ICAM-1、CD44的表达，并抑制p-P38、P38和p-MKK3/6的表达。结论褪黑素通过抑制胃癌细胞MMP-2、MMP-9、ICAM-1和CD44的表达从而抑制胃癌细胞的迁移和侵袭能力，抑制作用可能与p38MAPK信号通路有关。

Abstract

Objective To investigate the inhibitory effect of melatonin on the migration and invasion of gastric cancer cell and the underlying molecular mechanism. Methods Human gastric cancer SGC-7901 cells were treated with different concentrations of melatonin (0.1, 1, 2 and 4 mmol/L) for 24 hours, and the changes in the migration and invasion of gastric cancer cells were detected by scratch test and Transwell assay. The expressions of matrix metalloproteinase(MMP)-2 and MMP-9 in the supernatant were detected by ELISA kit. The changes of MMP-2, MMP-9, intercellular cell adhesion molecule-1(ICAM-1) and CD44 expressions were detected by using Real-time PCR. The protein expressions of ICAM-1, CD44, p-P38, P38 and phosphorylated mitogen-activated protein kinase kinase(p-MKK)3/6 were detected by Western blotting. Results Melatonin inhibited the migration and invasion of gastric cancer cells in a dose-dependent manner. Compared with the blank control group, melatonin reduced the expression of MMP-2, MMP-9, ICAM-1 and CD44, and inhibited the expressions of p-P38, P38 and p-MKK3/6 in gastric cancer cells. Conclusion Melatonin inhibits the migration and invasion of gastric cancer cells by inhibiting the expressions of MMP-2, MMP-9, ICAM-1 and CD44. Inhibition may be related to the p38MAPK signaling pathway. 

导出引用

徐丽金清东陈秀娇陈超郑伟男周瑞祥. 褪黑素抑制胃癌细胞系SGC-7901的迁移和侵袭[J]. 解剖学报. 2021, 52(5): 751-758 https://doi.org/10.16098/j.issn.0529-1356.2021.05.012

XU Li JIN Qing-dong CHEN Xiu-jiao CHEN Chao ZHENG Wei-nan ZHOU Rui-xiang. Melatonin inhibiting the migration and invasion of gastric cancer cell line SGC-7901#br#[J]. Acta Anatomica Sinica. 2021, 52(5): 751-758 https://doi.org/10.16098/j.issn.0529-1356.2021.05.012

中图分类号： R735.2

参考文献

［1］ Bray F, Ferlay J, Soerjomataram Ⅰ, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries ［J］.CA Cancer J Clin, 2018, 68(6):394-424. 
［2］ Mihmanli M, Ilhan E, Idiz UO, et al. Recent developments and innovations in gastric cancer［J］. World J Gastroenterol, 2016, 22(17):4307-4320.
［3］ Reiter RJ, Rosales-Corral SA, Tan DX, et al. Melatonin, a full service anti-cancer agent: inhibition of initiation, progression and metastasis ［J］. Int J Mol Sci, 2017, 18(4): 843. 
［4］ Cai R, Zhu Y, Wang KF, et al. 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. (in Chinese)
蔡蓉，朱瑜，王开放，等. 褪黑素体内外对胃癌Th1/Th2/Th17型细胞因子表达的影响［J］. 解剖学报,2019, 50(4): 471-476.
［5］ Li Z, Takino T, Endo Y, et al. Activation of MMP-9 by membrane type-1 MMP/MMP-2 axis stimulates tumor metastasis［J］.Cancer Sci, 2017, 108(3): 347-353.
［6］ Yang YL, Wang ZhY, Yang ZhY, et al. miR-125a-5p inhibits invasion and metastasis of breast cancer through PI3K/Akt/MMP signal pathway［J］. Chinese Pharmacological Bulletin, 2018, 34(8):1145-1149. (in Chinese)
杨玉玲，王照岩，杨志一，等. miR-125a-5p 通过 PI3K/Akt/MMP 信号通路抑制乳腺癌细胞的侵袭与转移［J］. 中国药理学通报, 2018, 34(8):1145-1149.
［7］ Wang HY, Wei HF, Wang WF, et al. Expression of ICAM-1 and 8-OHdG in renal cell carcinoma and its relationship with clinicopathological parameters［J］. Chinese Journal of Immunology, 2019, 35(8): 953-956. (in Chinese)
王宏英,魏海峰,王卫芳，等. ICAM-1和8-OHdG在肾癌组织中的表达及其与临床病理指标的关系［J］. 中国免疫学杂志，2019, 35(8): 953-956.
［8］ Xia P, Xu XY. Prognostic significance of CD44 in human colon cancer and gastric cancer: Evidence from bioinformatic analyses［J］. Oncotarget, 2016, 7(29): 45538-45546. 
［9］ Johansson N, Ala-aho R, Uitto Ⅴ, et al. Expression of collagenase-3 (MMP-13) and collagenase-1 (MMP-1) by transformed keratinocytes is dependent on the activity of p38 mitogen-activated protein kinase［J］. J Cell Sci, 2000, 113(2):227-235.
［10］ Huang X, Chen S, Xu L, et al. Genistein inhibits p38 map kinase activation, matrix metalloproteinase type 2, and cell invasion in human prostate epithelial cells［J］. Cancer Res, 2005, 65(8): 3470-3478.
［11］ Mao L, Yuan L, Slakey LM, et al. Inhibition of breast cancer cell invasion by melatonin is mediated through regulation of the p38 mitogen-activated protein kinase signaling pathway［J］. Breast Cancer Res, 2010, 12(6): R107. 
［12］ Xu L, Liu H, Zhang H, et al. Growth-inhibitory activity of melatonin on murine foregastric carcinoma (MFC) cells in vitro and the underlying molecular mechanism［J］. Anat Rec(Hoboken), 2013, 296(6):914-920.
［13］ Xu L, Jin QD, Gong X, et al. Inhibitory effect of melatonin on murine foregastric carcinoma cells via membrane receptors MT2［J］. Acta Anatomica Sinica, 2014, 45(3): 344-349. (in Chinese)
徐丽，金清东，宫喜,等. MT2 受体介导褪黑素对小鼠前胃癌细胞的抑制作用［J］. 解剖学报, 2014, 45(3): 344-349.
［14］ Liu H, Zhu Y, Zhu H, et al. Role of transforming growth factor β1 in the inhibition of gastriccancer cell proliferation by melatonin in vitro and in vivo［J］. Oncol Rep，2019, 42(2): 753-762. 
［15］ Luo JH, Song J, Zhang H, et al. Melatonin mediated Foxp3-downregulation decreases cytokines production via the TLR2 and TLR4 pathways in H. pylori infected mice［J］. Int Immunopharmacol, 2018, 64: 116-122. 
［16］ Song J, Ma SJ, Luo JH, et al. Downregulation of AKT and MDM2, melatonin induces apoptosis in AGS and MGC803 cells［J］.Anat Rec (Hoboken), 2019，302(9):1544-1551.
［17］ Wu ZY, Li JH，Zhan WH，et al. Lymph node micrometastasis and its correlation with MMP-2 expression in gastric carcinoma［J］. World J Gastroenter, 2006, 12(18)：2941-2944.
［18］ Liu WW, Chen Y, Xie H, et al. TIPE1 suppresses invasion and migration through down-regulating Wnt/β-catenin pathway in gastric cancer ［J］. J Cell Mol Med, 2018, 22(2): 1103-1117.
［19］ Ordo?ez R, Carbajo-Pescador S, Prieto-Dominguez N, et al. Inhibition of matrix metalloproteinase-9 and nuclear factor kappa B contribute to melatonin prevention of motility and invasiveness in HepG2 liver cancer cells［J］. J Pineal Res, 2014, 56(1):20-30.
［20］ Jung WC, Jang YF, Kim JH, et al. Expression of intercellular adhesion molecule-1 and E-selectin in gastric cancer and their clinical significance ［J］. J Gastric Cancer, 2012, 12(3): 140-148. 
［21］ Tian MM, Sun Y, Li ZW,et al. Polymorphisms of ICAM-1 are associated with gastric cancer risk and prognosis ［J］. World J Gastroenterol, 2012, 18(4): 368-374.
［22］ Huang KF. Experimental study on gambogic acid-induced gastric cancer cell apoptosis and anti-tumor metastasis［J］. Chinese Traditional and Herbal Drugs, 2010, 41(11):1823-1828. 
黄恺飞. 藤黄酸诱导胃癌细胞凋亡及抗肿瘤转移的实验研究［J］. 中草药，2010, 41(11):1823-1828. 
［23］ Kodama H, Murata S, Ishida M, et al. Prognostic impact of CD44-positive cancer stem-like cells at the invasive front of gastric cancer［J］. BJC, 2017, 116(2):186-194. 
［24］ Ibrahim HM, AbdElbary AM, Mohamed SY, et al. Prognostic value of cyclin D1 and CD44 expression in gastric adenocarcinoma ［J］. J Gastrointest Cancer，2019, 50(3):370-379. 
［25］ Wei Z, Chen X, Chen J, et al. RASSF10 is epigenetically silenced and functions as a tumor suppressor in gastric cancer［J］. Biochem Biophys Res Commun, 2013, 432(4):632-637.
［26］ Koul HK, Pal M, Koul S. Role of p38 MAP kinase signal transduction in solid tumors ［J］.Genes Cancer, 2013, 4(9-10): 342-359.
［27］ Huang QJ, Lan FH, Wang XT, et al.IL-1β-induced activation of p38 promotes metastasis in gastric adenocarcinoma via upregulation of AP-1/c-fos, MMP2 and MMP9 ［J］.Mol Cancer, 2014, 13(18):1-15.