藤黄酸通过核因子κB抑制剂激酶α/p65信号通路抑制人胃癌细胞系SGC-7901的侵袭

仝雷; 王世广; 杨占峰; 岳丽晓; 张玲玲; 王鹏

doi:10.16098/j.issn.0529-1356.2020.01.008

PDF(2392 KB)

解剖学报 ›› 2020, Vol. 51 ›› Issue (1) : 47-50. DOI: 10.16098/j.issn.0529-1356.2020.01.008

肿瘤生物学

藤黄酸通过核因子κB抑制剂激酶α/p65信号通路抑制人胃癌细胞系SGC-7901的侵袭

仝雷¹王世广²杨占峰³岳丽晓¹ 张玲玲¹王鹏^2*

作者信息 +

Gambogic acid suppresses invasion in human gastric carcinoma SGC-7901 cells by modulating inhibitor of nuclear factor kappa-B kinase α/p65 signaling pathway in vitro#br#

TONG Lei¹ WANG Shi-guang² YANG Zhan-feng³ YUE Li-xiao¹ZHANG Ling-ling¹WANG Peng^2*#br#

Author information +

文章历史 +

摘要

目的探讨藤黄酸（GA）对人胃癌SGC-7901细胞侵袭能力的影响及其机制。方法用不同浓度藤黄酸、核因子κB抑制剂激酶（IKK16）和阳性对照药物5-氟尿嘧啶作用人正常胃黏膜上皮GES-1细胞和人胃癌SGC-7901细胞48 h后，采用细胞计数试剂盒8（CCK-8）检测细胞活力，Transwell侵袭实验检测SGC-7901细胞的侵袭能力，免疫印迹法检测波形蛋白（vimentin）、基质金属蛋白酶2（MMP-2）和基质金属蛋白酶9（MMP-9）的蛋白表达水平以及IKKα和p65的蛋白磷酸化水平。结果藤黄酸可剂量依赖性地抑制SGC-7901细胞活力，半数抑制浓度（IC₅₀）分别为1.89 μmol/L，但对GES-1细胞活力无显著影响；5-氟尿嘧啶对GES-1和SGC-7901细胞均有抑制作用，IC50 分别为7.36 μmol/L和199.57 μmol/L。低剂量藤黄酸或IKK16可抑制SGC-7901细胞侵袭，下调MMP-2、MMP-9和vimentin的蛋白表达水平以及抑制IKKα和p65蛋白磷酸化，并且两者联合作用时抑制作用更强。

结论低剂量藤黄酸可在体外抑制人胃癌SGC-7901细胞侵袭，其机制可能与抑制IKKα/p65信号通路，继而下调MMP-2、MMP-9和vimentin蛋白表达水平相关。

Abstract

Objective To investigate the effect of gambogic acid (GA) on invasion in human gastric carcinoma SGC-7901 cells and its possible mechanism. Methods Cell counting kit-8(CCK-8) assay was performed to detect the effects of GA, inhibitor of nuclear factor kappa-B kinase(IKK)16 and 5-fluorouracil (5-FU) on cell activity of GES-1 and SGC-7901 cells. Cell invasion was assessed with Transwell invasion assay. Western blotting was used to analyze the protein levels of vimentin, matrix metalloproteinase 2 (MMP-2) and MMP-9 and protein phosphorylation of IKKα and p65. Results The cell activity was significantly decreased in SGC-7901 cells treated with GA in a dose-dependent manner with a half inhibiton concentration(IC50) value of 1.89 μmol/L. But GA had no significant influence on cell viability of GES-1 cells. Meanwhile, 5-FU reduced the cell activity of GES-1 and SGC-7901 cells with IC50 values of 7.36 μmol/L and 199.57 μmol/L respectively. Low-dose GA and IKK16 impaired separately the ability of invasion in SGC-7901 cells, and down-regulated the protein levels of MMP-2, MMP-9 and vimentin, and inhibited phosphorylation of IKKα and p65, while a stronger inhibition was showed when the combination of GA and IKK16 was used. Conclusion Low-dose GA might inhibit invasion of SGC-7901 cells via IKKα/p65 signaling pathway.

导出引用

仝雷王世广杨占峰岳丽晓张玲玲王鹏. 藤黄酸通过核因子κB抑制剂激酶α/p65信号通路抑制人胃癌细胞系SGC-7901的侵袭[J]. 解剖学报. 2020, 51(1): 47-50 https://doi.org/10.16098/j.issn.0529-1356.2020.01.008

TONG Lei WANG Shi-guang YANG Zhan-feng YUE Li-xiao ZHANG Ling-ling WANG Peng. Gambogic acid suppresses invasion in human gastric carcinoma SGC-7901 cells by modulating inhibitor of nuclear factor kappa-B kinase α/p65 signaling pathway in vitro#br#[J]. Acta Anatomica Sinica. 2020, 51(1): 47-50 https://doi.org/10.16098/j.issn.0529-1356.2020.01.008

中图分类号： R735.2

参考文献

［1］ Liang L, Zhang Z. Gambogic acid inhibits malignant melanoma cell proliferation through mitochondrial p66shc/ROS-p53/Bax-mediated apoptosis ［J］. Cell Physiol Biochem, 2016, 38(4):1618-1630.

［2］ Yan X, Yang Y, He L, et al. Gambogic acid grafted low molecular weight heparin micelles for targeted treatment in a hepatocellular carcinoma model with an enhanced anti-angiogenesis effect ［J］. Int J Pharm, 2017, 522(1-2):110-118.

［3］ Tong L, Wang LJ, Yuan L. Enhancing effect of gambogic acid on the sensibility of human gastric carcinoma SGC7901/DDP cells to cisplatin ［J］. Acta Anatomica Sinica, 2018, 49(3): 337-41. (in Chinese)

仝雷, 王丽君, 袁磊. 藤黄酸增强人胃癌SGC7901/DDP细胞对顺铂的敏感性［J］. 解剖学报, 2018, 49(3): 337-341.

［4］ Li J, Wang X, Shao Y, et al. A novel exploration of a combination of gambogic acid with TiO2 nanofibers: the photodynamic effect for HepG2 cell proliferation ［J］. Materials (Basel), 2014, 7(9):6865-6878.

［5］ Xin ZF, Shen CC, Tao LJ, et al. Gambogic acid inhibits invasion of osteosarcoma via upregulation of TIMP-1 ［J］. Int J Mol Med, 2013, 31(1):105-112.

［6］ Diao LY. Mechanism research of traditional Chinese medicine monomer gambogic acid in suppressing epithelial-mesenchymal transition of human gastric cancer cells by regulating the function of miRNA-590-5p ［D］. Nanjing: Nanjing University of Chinese Medicine, 2017. (in Chinese)

刁凌云. 中药单体藤黄酸通过调控miRNA-590-5p的功能抑制人胃癌细胞上皮-间质转移的机制研究［D］. 南京:南京中医药大学, 2017.

［7］ 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. (in Chinese)

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.

［8］ Ren J, Li L, Wang Y, et al. Gambogic acid induces heme oxygenase-1 through Nrf2 signaling pathway and inhibits NF-κB and MAPK activation to reduce inflammation in LPS-activated RAW264.7 cells ［J］. Biomed Pharmacother, 2018, 109(2018):555-562.

［9］ Na D, Aijie H, Bo L, et al. Gambogic acid exerts cardioprotective effects in a rat model of acute myocardial infarction through inhibition of inflammation, iNOS and NF-κB/p38 pathway ［J］. Exp Ther Med, 2018, 15(2):1742-1748.

［10］Cui J, Gong R, Hu S, et al. Gambogic acid ameliorates diabetes-induced proliferative retinopathy through inhibition of the HIF-1α/VEGF expression via targeting PI3K/AKT pathway ［J］. Life Sci, 2018, 192(2018):293-303.

［11］Wen J, Pei H, Wang X, et al. Gambogic acid exhibits anti-psoriatic efficacy through inhibition of angiogenesis and inflammation ［J］. J Dermatol Sci, 2014, 74(3):242-250.

［12］Li C, Huo B, Wang Y, et al. Downregulation of microRNA-92b-3p suppresses proliferation, migration, and invasion of gastric cancer SGC-7901 cells by targeting Homeobox D10 ［J］. J Cell Biochem, 2019, 120(10):17405-17412.

［13］Gao G, Bian Y, Qian H, et al. Gambogic acid regulates the migration and invasion of colorectal cancer via microRNA-21-mediated activation of phosphatase and tensin homolog ［J］. Exp Ther Med, 2018, 16(3):1758-1765.

［14］Otsuki S, Inokuchi M, Enjoji M, et al. Vimentin expression is associated with decreased survival in gastric cancer ［J］. Oncol Rep, 2011, 25(5):1235-1242.

［15］Zhu Z, Rong Z, Luo Z, et al. Circular RNA circNHSL1 promotes gastric cancer progression through the miR-1306-3p/SIX1/vimentin axis ［J］. Mol Cancer, 2019, 18(1):126.

［16］Park MS, Kim NH, Kang CW, et al. Antimetastatic effects of gambogic acid are mediated via the actin cytoskeleton and NF-κB pathways in SK-HEP1 cells ［J］. Drug Dev Res, 2015, 76(3):132-142.

［17］Xu YH, Li ZL, Qiu SF. IFN-γ Induces gastric cancer cell proliferation and metastasis through upregulation of integrin β3-mediated NF-κB signaling ［J］. Transl Oncol, 2018, 11(1):182-192.

［18］Yang Y, Cai H, Yuan X, et al. Efficient targeting drug delivery system for lewis lung carcinoma, leading to histomorphological abnormalities restoration, physiological and psychological statuses improvement, and metastasis inhibition ［J］. Mol Pharm, 2018, 15(5):2007-2016.

［19］Li C, Qi Q, Lu N, et al. Gambogic acid promotes apoptosis and resistance to metastatic potential in MDA-MB-231 human breast carcinoma cells ［J］. Biochem Cell Biol, 2012, 90(6):718-730.

［20］Zhao J,Qi Q,Yang Y, et al. Inhibition of alpha(4) integrin mediated adhesion was involved in the reduction of B16-F10 melanoma cells lung colonization in C57BL/6 mice treated with gambogic acid ［J］. Eur J Pharmacol, 2008, 89(1-3):127-131.