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7-O-丁二酰大环内酯菌素A对人肺癌细胞H460的抑制作用及其机制

杨培树, 郝文立

杨培树, 郝文立. 7-O-丁二酰大环内酯菌素A对人肺癌细胞H460的抑制作用及其机制[J]. 中国药科大学学报, 2017, 48(1): 82-88. DOI: 10.11665/j.issn.1000-5048.20170113
引用本文: 杨培树, 郝文立. 7-O-丁二酰大环内酯菌素A对人肺癌细胞H460的抑制作用及其机制[J]. 中国药科大学学报, 2017, 48(1): 82-88. DOI: 10.11665/j.issn.1000-5048.20170113
YANG Peishu, HAO Wenli. Inhibitory effect and its mechanism of 7-O-succinyl macrolactin A against cell proliferation, invasion and migration in human lung cancer H460 cells[J]. Journal of China Pharmaceutical University, 2017, 48(1): 82-88. DOI: 10.11665/j.issn.1000-5048.20170113
Citation: YANG Peishu, HAO Wenli. Inhibitory effect and its mechanism of 7-O-succinyl macrolactin A against cell proliferation, invasion and migration in human lung cancer H460 cells[J]. Journal of China Pharmaceutical University, 2017, 48(1): 82-88. DOI: 10.11665/j.issn.1000-5048.20170113

7-O-丁二酰大环内酯菌素A对人肺癌细胞H460的抑制作用及其机制

Inhibitory effect and its mechanism of 7-O-succinyl macrolactin A against cell proliferation, invasion and migration in human lung cancer H460 cells

  • 摘要: 探讨7-O-丁二酰大环内酯菌素A对人肺癌细胞侵袭转移的抑制作用及其机制。7-O-丁二酰大环内酯菌素A处理人肺癌细胞H460后,采用MTS、细胞黏附、Transwell和划痕实验观察7-O-丁二酰大环内酯菌素A对细胞生长、体外黏附能力及侵袭转移的影响,流式细胞术检测细胞周期和凋亡的变化,RT-PCR和Western blot检测7-O-丁二酰大环内酯菌素A对β-catenin、c-Myc、Cyclin D1、vimentin、N-cadherin、CD44、integrin β1、bcl-2、Survivin和MMP-2/9的mRNA和蛋白表达的影响以及AKT和mTOR的磷酸化的变化。结果表明:7-O-丁二酰大环内酯菌素A显著抑制H460细胞的体外增殖和体外黏附,诱导细胞发生凋亡,且抑制细胞体外迁移和侵袭能力。Western blot和Real-time PCR结果显示,7-O-丁二酰大环内酯菌素A下调细胞中Bcl-2、Survivin、β-catenin、c-Myc、Cyclin D1、vimentin、N-cadherin、CD44、integrin β1和MMP-2/9的表达,以及AKT和mTOR的磷酸化。7-O-丁二酰大环内酯菌素A可抑制人肺癌细胞H460的体外生长,并抑制其体外黏附和侵袭转移能力。
    Abstract: This study aimed at investigating the effects and mechanisms of 7-O-succinyl macrolactin A in inhibiting human lung cancer. After treatment of human lung cancer cell lines H460 with 7-O-succinyl macrolactin A, MTS assay was employed to determine cell proliferation; crystal violet staining was used to detect cell adhesion of H460; transwell chamber assay and wound healing assay were performed to evaluate cell invasion and migration; and flow cytometry assay was adopted to evaluate cell cycle. Western blotting and real-time PCR were also employed to determine the expression of β-catenin, c-Myc, Cyclin D1, vimentin, N-cadherin, CD44, integrin β1, Bcl-2, Survivin and MMP-2/9. The phosphorylation of AKT and mTOR was determined as well. In vitro proliferation of H460 was inhibited significantly by 7-O-succinyl macrolactin A. Cell adhesion, invasion and migration abilities were also attenuated. Western blot and real-time PCR showed that the expressions of β-catenin, c-Myc, cyclin D1, vimentin, N-cadherin, CD44, integrin β1, Bcl-2, Survivin and MMP-2/9 were down-regulated by 7-O-succinyl macrolactin A. It was also found that phosphorylation of AKT and mTOR was inhibited by 7-O-succinyl macrolactin A. 7-O-succinyl macrolactin A can inhibit the in vitro growth and invasion of human lung cancer cell lines H460.
  • [1] Gao Y,Zhao Y,Yao J,et al.Wogonin suppresses human alveolar adenocarcinoma cell A549 invasion and metastasis induced by IL-6[J].J China Pharm Univ(中国药科大学学报),2015,46(3):345-349.
    [2] Santos AA,Matos AJ.Advances in the understanding of the clinically relevant genetic pathways and molecular aspects of canine mammary tumours.Part 2:invasion,angiogenesis,metastasis and therapy[J].Vet J,2015,205(2):144-153.
    [3] Romero-Tabarez M,Jansen R,Sylla M,et al.7-O-malonyl macrolactin A,a new macrolactin antibiotic from Bacillus subtilis active against methicillin-resistant Staphylococcus aureus,Vancomycin-resistant enterococci,and a small-colony variant of Burkholderia cepacia[J].Antimicrob Agents Chemother,2006,50(5):1701-1709.
    [4] Kim DH,Kim HK,Kim KM,et al.Antibacterial activities of macrolactin A and 7-O-succinyl macrolactin A from Bacillus polyfermenticus KJS-2 against vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus[J].Arch Pharm Res,2011,34(1):147-152.
    [5] Wu X,Zhu Y,Yan H,et al.Isothiocyanates induce oxidative stress and suppress the metastasis potential of human non-small cell lung cancer cells[J].BMC Cancer,2010,9(10):269.
    [6] Reck M,Popat S,Reinmuth N,et al.Metastatic non-small-cell lung cancer:ESMO Clinical Practice Guidelines for diagnosis,treatment and follow-up[J].Ann Oncol,2014,25(Suppl 3):iii27-39.
    [7] Spano D,Heck C,De Antonellis P,et al.Molecular networks that regulate cancer metastasis[J].Semin Cancer Biol,2012,22(3):234-249.
    [8] Han B,Guo Z,Ma Y,et al.Association of GSTP1 and XRCC1 gene polymorphisms with clinical outcome of advanced non-small cell lung cancer patients with cisplatin-based chemotherapy[J].Int J Clin Exp Pathol,2015,8(4):4113-4119.
    [9] Al-Taweel AM,Perveen S,Fawzy GA,et al.Cytotoxicity assessment of six different extracts of abelia triflora leaves on A549 human lung adenocarcinoma cells[J].Asian Pac J Cancer Prev,2015,16(11):4641-4645.
    [10] Regmi SC,Park SY,Kim SJ,et al.The anti-tumor activity of succinyl macrolactin A is mediated through the β-catenin destruction complex via the suppression of tankyrase and PI3K/Akt[J].PLoS One,2015,10(11):e0141753.
    [11] Kang Y,Regmi SC,Kim MY,et al.Anti-angiogenic activity of macrolactin A and its succinyl derivative is mediated through inhibition of class I PI3K activity and its signaling[J].Arch Pharm Res,2015,38(2):249-260.
    [12] Zhao R,Chen M,Jiang Z,et al.Platycodin-D induced autophagy in non-small cell lung cancer cells via PI3K/Akt/mTOR and MAPK signaling pathways[J].J Cancer,2015,6(7):623-631.
    [13] Gu CP,Que FC,Li YL,et al.Cisplatin inhibits survival of human esophageal squamous carcinoma cells via p53 activation[J].J China Pharm Univ(中国药科大学学报),2016,47(1):90-94.
    [14] Liu W, Ren H, Ren J, et al. The role of EGFR/PI3K/Akt/cyclinD1 signaling pathway in acquired middle ear cholesteatoma[J].Mediators Inflamm,2013:651207.
    [15] Ku JH,Seo SY,Kwak C,et al.The role of survivin and Bcl-2 in zinc-induced apoptosis in prostate cancer cells[J].Urol Oncol,2012,30(5):562-568.
    [16] Shay G,Lynch CC,Fingleton B.Moving targets:emerging roles for MMPs in cancer progression and metastasis[J].Matrix Biol,2015,44-46:200-206.
    [17] Wang R,Ke ZF,Wang F,et al.GOLPH3 overexpression is closely correlated with poor prognosis in human non-small cell lung cancer and mediates its metastasis through upregulating MMP-2 and MMP-9[J].Cell Physiol Biochem,2015,35(3):969-982.
    [18] Zhang H,Guo M,Chen JH,et al.Osteopontin knockdown inhibits αv,β3 integrin-induced cell migration and invasion and promotes apoptosis of breast cancer cells by inducing autophagy and inactivating the PI3K/Akt/mTOR pathway[J].Cell Physiol Biochem,2014,33(4):991-1002.
    [19] Park S,Regmi SC,Park SY,et al.Protective effect of 7-O-succinyl macrolactin A against intestinal inflammation is mediated through PI3-kinase/Akt/mTOR and NF-κB signaling pathways[J].Eur J Pharmacol,2014,735:184-192.
    [20] Ponnusamy MP,Seshacharyulu P,Lakshmanan I,et al.Emerging role of mucins in epithelial to mesenchymal transition[J].Curr Cancer Drug Targets,2013,13(9):945-956.
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  • 刊出日期:  2017-02-24

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