Impact of evodiamine on proliferation of human hepatocellular carcinoma HepG2 cells
-
摘要: 目的探讨吴茱萸碱(EVO)对人肝癌HepG2细胞增殖的影响及作用机制。方法以人肝癌细胞株(HepG2细胞)为受试细胞, 实验设对照组、吴茱萸碱5.0、12.5、25.0、50.0、100.0 μmol/L组, 采用噻唑蓝法检测HepG2细胞增殖抑制率, 划痕实验检测HepG2细胞伤痕愈合率, Western blot检测HepG2细胞基质金属蛋白酶9(matrix metalloproteinase-9,MMP-9)、增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)蛋白。结果吴茱萸碱对HepG2细胞增殖抑制率明显高于对照组, 呈现时间-剂量依赖关系(P<0.05);与对照组比较, 吴茱萸碱5.0、25.0、50.0 μmol/L组HepG2细胞24、48 h伤痕愈合率[分别为(23.31±1.03)%、(10.37±1.06)%、(7.92±1.40)%和(13.86±5.57)%、(1.78±3.08)%、0%]明显下降, 差异有统计学意义(P<0.05);与对照组比较, 吴茱萸碱5.0、25.0、50.0 μmol/L组HepG2细胞24 h MMP-9、PCNA蛋白表达量[分别为(0.53±0.020)、(0.35±0.020)、(0.21±0.015)与(0.76±0.032)、(0.66±0.01)、(0.59±0.015)]降低, 差异有统计学意义(P<0.05)。结论吴茱萸碱可明显抑制HepG2细胞增殖及远处迁徙, 其机制可能与吴茱萸碱下调MMP-9、PCNA蛋白有关。
-
关键词:
- 吴茱萸碱 /
- 人肝癌细胞株(HepG2细胞) /
- 增殖 /
- 基质金属蛋白酶9(MMP-9) /
- 增殖细胞核抗原(PCNA)
Abstract: ObjectiveTo study the effect and mechanism of evodiamine on proliferation of human hepatocellular carcinoma(HepG2) cells.MethodsHepG2 cells were treated with evodiamin at dosages of 5.0,12.5,25.0,50.0,and 100.0 umol/L.The cell proliferation was assayed by using 3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide(MTT) method.The ability of cicatrization was analyzed with scratch wounds healing.The expressions of matrix metalloproteinase-9(MMP-9),proliferating cell nuclear antigen(PCNA) in HepG2 cells were assessed with Western blot.ResultsThe proliferation inhibition rate of evodiamine-treated groups was higher than that of the control group in a dose- and time-effect manner(P<0.05).Evodiamine could significantly inhibit cicatrization rate of HepG2 cells compared with the control group,with the cicatrization rates of 23.31±1.03%,10.37±1.06%,and 7.92±1.40% at 24 hours and 13.86±5.57%,1.78±3.08,and 0±0% at 48 hours for the groups with the dosage of 5.0,25.0,and 50.0 μmol/L,respectively(all P<0.05).The expression levels of MMP-9 and PCNA were down-regulated(0.53±0.020,0.35±0.020,and 0.21±0.015 and 0.76±0.032,0.66±0.01,and 0.59±0.015 for the groups with the dosage of 5.0,25.0,and 50.0 μmol/L)(all P<0.05).ConclusionEvodiamine can inhibit proliferation of HepG2 cells and the mechanism of the effect may be related to down-regulations of MMP-9 and PCNA proteins.-
Key words:
- evodiamine /
- HepG2 cell /
- proliferation /
- MMP-9 /
- PCNA
-
[1] 尹元元,闫利华,张启伟,等.吴茱萸及其习用品药材中7个成分的HPLC含量测定[J].中国中药杂志,2014(14):2693-2698. [2] Hong JY,Park SH,Min HY,et al.Anti-proliferative effects of evodiamine in human lung cancer cells[J].J Cancer Prev, 2014, 19(1):7-13. [3] Yang J1,Cai X,Lu W,et al.Enhancement of apoptosis of human hepatocellular carcinoma SMMC-7721 cells through synergy of berberine and evodiamine[J].Phytomedicine, 2008, 15(12):1062-1068. [4] El-Serag HB,Marrero JA,Rudolph L,et al.Diagnosis and treatment of hepatocellular carcinoma[J].Gastroenterology, 2008, 134:1752-1763. [5] Monvoisin A,Neaud V,De Ledinghen V,et al.Direct evidence that hepatocyte growth factor induced invasion of hepatocellular carcinoma cells is mediated by urokinase[J].J Hapatol, 1999,30:511-518. [6] Lin H,van den Esschert J,Liu C,et al.Systematic review of hepatocellular carcinoma in China and other regions[J].J Gastroenterol Hepatol,2011,26(1):28-35. [7] Lau WY,Lai EC.Salvage surgery following downstaging of unresectable hepatocellular carcinoma-a strategy to increase respectability[J].Ann Surg Oncol,2007,14(12):3301-3309. [8] Shi HL,Wu XJ,Liu Y,et al.Berberine counteracts enhanced IL-8 expression of AGS cells induced by evodiamine[J].Life Sci, 2013, 93(22):830-839. [9] Liu AJ,Wang SH,Chen KC,et al.Evodiamine,a plant alkaloid,induces calcium/JNK-mediated autophagy and calcium/mitochondria-mediated apoptosis in human glioblastoma cells[J].Chem Biol Interact, 2013, 205(1):20-28. [10] Wang KL,Hsia SM,Yeh JY,et al.Anti-proliferative effects of evodiamine on human breast cancer cells[J].PLoS One, 2013, 8(6):1-8. [11] 王青,梁惠,刘颖, 等.海兔素对小鼠H22移植瘤侵袭及免疫调节影响[J].中国公共卫生,2014(10):1265-1267. [12] Westermarck J.Regulation of matrix metalloproteinase expression in tumor invasion[J].FASEB J,1999, 13(8):781-792. [13] Zheng H,Takahashi H,Murai Y,et al.Expressions of MMP-2,MMP-9 and VEGF are closely linked to growth,invasion,metastasis and angiogenesis of gastric carcinoma[J].Anticancer Res, 2006, 26(5A):3579-3583.
点击查看大图
计量
- 文章访问数: 1083
- HTML全文浏览量: 275
- PDF下载量: 83
- 被引次数: 0