萝卜硫素对胃癌细胞生物学特征的影响及其机制研究
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摘要
目的:观察萝卜硫素对胃癌细胞(SGC7901)生物学特征的影响,并探讨其可能的作用机制。方法:采用CCK8、细胞划痕及Transwell侵袭试验检测萝卜硫素对SGC7901细胞增殖、迁移及侵袭能力的影响;酶联免疫吸附实验(ELISA)检测萝卜硫素对SGC7901细胞培养液上清中白细胞介素6(IL-6)、白细胞介素8(IL-8)和肿瘤坏死因子α(TNF-α)水平的影响;蛋白免疫印迹(Western blot)方法检测蛋白激酶B(Akt)、核因子-κB(NF-κB)、磷酸化蛋白激酶B(p-Akt)、磷酸化核因子-κB(p-NF-κB)蛋白的表达。结果:与对照组相比,萝卜硫素呈浓度、时间依赖性的抑制SGC7901细胞增殖,细胞迁移距离明显增大,穿膜细胞数明显增多(P <0. 05);与对照组比较,不同剂量萝卜硫素组中炎症因子IL-6、IL-8和TNF-α含量显著降低,而且Akt、NF-κB、p-Akt及p-NF-κB蛋白表达水平也明显受到抑制,差异有统计学意义(P <0. 05)。结论:萝卜硫素可能通过抑制PI3K/Akt信号通路活化进而降低SGC7901细胞增殖、迁移及侵袭能力。
Objective: To study the effect of sulforaphane on biological activity of gastric cancer cells( SGC7901) and its related mechanisms. Methods: CCK8 assay was used to measure cell proliferation. Wound healing assay and Transwell assay were used to analyze the migration and invasion of SGC7901 cells. ELISA was used to determine the levels of IL-6,IL-8 and TNF-α. Western blot was used to analyze the expression levels of Akt,NF-κB,p-Akt and p-NF-κB. Results: After the treatment with sulforaphane,the proliferation of SGC7901 cells was significantly decreased compared with that in the control group in time-and concentration-dependent manners( P < 0. 05); the cell migration distance was markedly decreased,and the number of transmembrance cells was greatly decreased( P < 0. 05). Compared with those in the control group,the levels of IL-6,IL-8 and TNF-α in the cells after the treatment with sulforaphane were significantly decreased,and the expression levels of Akt,NF-κB,p-Akt and p-NF-κB were also greatly decreased( P <0. 05). Conclusion: Sulforaphane can inhibit the proliferation,migration and invasion of SGC7901 cells via suppressing the activation of PI3 K/Akt signaling pathway.
Objective: To study the effect of sulforaphane on biological activity of gastric cancer cells( SGC7901) and its related mechanisms. Methods: CCK8 assay was used to measure cell proliferation. Wound healing assay and Transwell assay were used to analyze the migration and invasion of SGC7901 cells. ELISA was used to determine the levels of IL-6,IL-8 and TNF-α. Western blot was used to analyze the expression levels of Akt,NF-κB,p-Akt and p-NF-κB. Results: After the treatment with sulforaphane,the proliferation of SGC7901 cells was significantly decreased compared with that in the control group in time-and concentration-dependent manners( P < 0. 05); the cell migration distance was markedly decreased,and the number of transmembrance cells was greatly decreased( P < 0. 05). Compared with those in the control group,the levels of IL-6,IL-8 and TNF-α in the cells after the treatment with sulforaphane were significantly decreased,and the expression levels of Akt,NF-κB,p-Akt and p-NF-κB were also greatly decreased( P <0. 05). Conclusion: Sulforaphane can inhibit the proliferation,migration and invasion of SGC7901 cells via suppressing the activation of PI3 K/Akt signaling pathway.
引文
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2 Balakrishnan M,George R,Sharma A,et al.Changing trends in stomach cancer throughout the world[J].Curr Gastroenterol Rep,2017,19(8):36-41
3王丽,张洪,范月莹,等.甲磺酸伊马替尼对胃癌细胞HGC-27增殖、凋亡及迁移的影响[J].中国药师,2018,21(11):1916--1919
4朱俊,林俊,陈善明,等.复方苦参注射液辅助化疗对晚期胃癌的疗效观察[J].中国药师,2015,18(12):2117-2119
5 Mao Z,Zhou J,Luan J,et al.Tamoxifen reduces P-gpmediated multidrug resistance via inhibiting the PI3K/Akt signaling pathway in ER-negative human gastric cancer cells[J].Biomed Pharmacother,2014,68(2):179-183
6覃正碧,毛卫林.萝卜硫素对肾小管上皮细胞氧化应激及Nrf2/HO-1信号通路的影响[J].中国药师,2017,20(5):809-812
7 Wang L,Tian Z,Yang Q,et al.Sulforaphaneinhibits thyroid cancer cell growth and invasiveness through the reactive oxygen speciesdependent pathway[J].Oncotarget,2015,6(28):25917-25931
8 Alumkal JJ,Slottke R,Schwartzman J,et al.A phaseⅡstudy of sulforaphane-rich broccoli sprout extracts in men with recurrent prostate cancer[J].Invest New Drugs,2015,33(2):480-489
9贺云冲,贾侃,王川,等.西兰花提取物萝卜硫素抑制胃癌和胰腺癌的生长与侵袭[J].科技通报,2015,31(9):62-69
10朱涛,王永翠.萝卜硫素通过Traf6/TAK1信号通路介导人胃癌细胞凋亡的机制研究[J].天津中医药,2018,35(9):710-713
11 Yan Y,Wang LF,Wang RF.Role of cancer-associated fibroblasts in invasion and metastasis of gastric cancer[J].World J Gastroenterol,2015,21(33):9717-9126
12 Hu S,Zheng Q,Wu H,et al.miR-532 promoted gastric cancer migration and invasion by targeting NKD1[J].Life Sci,2017,177:15-19
13 Sánchez-Zauco N,Torres J,Gómez A,et al.Circulating blood levels of IL-6,IFN-γ,and IL-10 as potential diagnostic biomarkers in gastric cancer:a controlled study[J].BMC Cancer,2017,17(1):384-392
14 Zhang W,Gu J,Chen J,et al.Interaction with neutrophils promotes gastric cancer cell migration and invasion by inducing epithelial-mesenchymal transition[J].Oncol Rep,2017,38(5):2959-2966
15 von Karstedt S,Conti A,Nobis M,et al.Cancer cell-autonomous TRAIL-R signaling promotes KRAS-driven cancer progression,invasion,and metastasis[J].Cancer Cell,2015,27(4):561-573
16 Zhou Y,Li S,Li J,et al.Effect of microRNA-135a on cell proliferation,migration,invasion,apoptosis and tumor angiogenesis through the IGF-1/PI3K/Akt signaling pathway in non-small cell lung cancer[J].Cell Physiol Biochem,2017,42(4):1431-1446
17 Zhou Y,Gu P,Li J,et al.Suppression of STIM1 inhibits the migration and invasion of human prostate cancer cells and is associated with PI3K/Akt signaling inactivation[J].Oncol Rep,2017,38(5):2629-2636
18 Yan J,Dang Y,Liu S,et al.LncRNA HOTAIR promotes cisplatin resistance in gastric cancer by targeting miR-126 to activate the PI3K/AKT/MRP1 genes[J].Tumour Biol,2016,32(11):21-33
19 Wu L,Zhang X,Zhang B,et al.Exosomes derived from gastric cancer cells activate NF-κB pathway in macrophages to promote cancer progression[J].Tumour Biol,2016,37(9):12169-12180
20 Pawlik A,Wiczk A,Kaczyńska A,et al.Sulforaphane inhibits growth of phenotypically different breast cancer cells[J].Eur J Nutr,2013,52(8):1949-1958