芒果甙对白血病HL-60细胞侵袭能力的影响
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摘要
目的观察芒果甙对人急性髓细胞白血病HL-60细胞黏附和侵袭能力的影响,并对其作用机制进行初步探讨,以进一步阐明芒果甙抗白血病的作用机制。
方法用细胞黏附实验和Minicell小室体外细胞侵袭实验法测定不同浓度芒果甙作用HL-60细胞24、48小时后对其黏附和侵袭能力的影响。用RT-PCR法检测芒果甙作用HL-60细胞后对肿瘤侵袭转移相关信号分子FAK、CXCR4、MMP-2的mRNA表达的影响。
结果①细胞黏附实验发现,用20-250μmol/L芒果甙作用HL-60细胞24、48小时后,芒果甙抑制HL-60细胞的黏附能力随着药物浓度增加和作用时间延长逐渐增强。②侵袭小室实验发现,用20-250μmol/L芒果甙作用HL-60细胞24、48小时后,可抑制HL-60细胞穿透Minicell小室PVPF滤膜的细胞数,随着药物浓度增加和作用时间延长其穿透滤膜的细胞数明显减少。③用20-250μmol/L芒果甙作用HL-60细胞24、48小时后,可降低FAK、CXCR4、MMP-2的mRNA表达量;其中FAK的mRNA表达量呈明显的量效和时效关系,低浓度芒果甙(<40μmol/L)作用HL-60细胞24小时下调CXCR-4和MMP-2的mRNA水平不明显(P>0.05),至高浓度时(≥40μmol/L)HL-60细胞CXCR4和MMP-2 mRNA表达量开始减少,分别至160μmol/L和200μmol/L时,mRNA表达量下降至最低。高浓度芒果甙和随着作用时间的延长,芒果甙对CXCR4和MMP-2的mRNA相对表达量未有明显下降,但与未加药组对照组相比,差异均有统计学性意义(P<0.05)。
结论芒果甙能显著抑制白血病HL-60细胞的侵袭能力,其机制可能与抑制细胞黏附能力和下调FAK、CXCR4、MMP-2的mRNA表达有关。
Objective To study the effect of mangiferin on the adhesion and invasive ability of human acute myeloid leukemia HL-60 cells and its possible mechanism, further to study the melocular mechanism for treating leukemia.
Methods The cell adhesion assay and the Minicell chamber assay were performed to determine the effect with different concentration of mangiferin for 24 and 48 hours on the adhesion and invasive ability of HL-60 cells. The expression of FAK、CXCR4 and MMP-2 mRNA was detected by semi-quantitative RT-PCR.
Results①The results of cell adhesion experiment showed that the cell adhesion ability inhibited in HL-60 cells in dose-time dependent manner after treated by 20-250μmol/L mangiferin for 24、48 hours.②Mangiferin efficiently suppressed the results of Chamber experiment showed that the number of cells under micro-membrane decreased in HL-60 cells in dose-time dependent manner after treated by 20-250μmol/ L mangiferin for 24、48 hours.③Mangiferin efficiently suppressed the expression of FAK、CXCR4 and MMP-2 mRNA in HL-60 cells, the expression of FAK mRNA in dose-time dependent manner. The expression of CXCR4 and MMP-2 mRNA not statistical significance after treament with mangiferin for 24 hours exposure of HL-60 cells from 20μmol/L. It efficiently suppressed from 40μmol/L and the proportion of which with 160μmol/L and 200μmol/L mangiferin was significantly lower than that occurring in untreated cells. It’s not statistical significance that expression of CXCR4 and MMP-2 genes treated with mangiferin for 48 hours and high concentration but it’s statistical significance compare with that occurring in untreated cells. (P<0.05).
Conclusion Mangiferin can inhibits obviously the invasive ability of leukemia HL-60 cells and its mechanism may be related to inhibit obviously the capability of adhesion and reduce the expression of FAK CXCR4 and MMP-2 mRNA.
方法用细胞黏附实验和Minicell小室体外细胞侵袭实验法测定不同浓度芒果甙作用HL-60细胞24、48小时后对其黏附和侵袭能力的影响。用RT-PCR法检测芒果甙作用HL-60细胞后对肿瘤侵袭转移相关信号分子FAK、CXCR4、MMP-2的mRNA表达的影响。
结果①细胞黏附实验发现,用20-250μmol/L芒果甙作用HL-60细胞24、48小时后,芒果甙抑制HL-60细胞的黏附能力随着药物浓度增加和作用时间延长逐渐增强。②侵袭小室实验发现,用20-250μmol/L芒果甙作用HL-60细胞24、48小时后,可抑制HL-60细胞穿透Minicell小室PVPF滤膜的细胞数,随着药物浓度增加和作用时间延长其穿透滤膜的细胞数明显减少。③用20-250μmol/L芒果甙作用HL-60细胞24、48小时后,可降低FAK、CXCR4、MMP-2的mRNA表达量;其中FAK的mRNA表达量呈明显的量效和时效关系,低浓度芒果甙(<40μmol/L)作用HL-60细胞24小时下调CXCR-4和MMP-2的mRNA水平不明显(P>0.05),至高浓度时(≥40μmol/L)HL-60细胞CXCR4和MMP-2 mRNA表达量开始减少,分别至160μmol/L和200μmol/L时,mRNA表达量下降至最低。高浓度芒果甙和随着作用时间的延长,芒果甙对CXCR4和MMP-2的mRNA相对表达量未有明显下降,但与未加药组对照组相比,差异均有统计学性意义(P<0.05)。
结论芒果甙能显著抑制白血病HL-60细胞的侵袭能力,其机制可能与抑制细胞黏附能力和下调FAK、CXCR4、MMP-2的mRNA表达有关。
Objective To study the effect of mangiferin on the adhesion and invasive ability of human acute myeloid leukemia HL-60 cells and its possible mechanism, further to study the melocular mechanism for treating leukemia.
Methods The cell adhesion assay and the Minicell chamber assay were performed to determine the effect with different concentration of mangiferin for 24 and 48 hours on the adhesion and invasive ability of HL-60 cells. The expression of FAK、CXCR4 and MMP-2 mRNA was detected by semi-quantitative RT-PCR.
Results①The results of cell adhesion experiment showed that the cell adhesion ability inhibited in HL-60 cells in dose-time dependent manner after treated by 20-250μmol/L mangiferin for 24、48 hours.②Mangiferin efficiently suppressed the results of Chamber experiment showed that the number of cells under micro-membrane decreased in HL-60 cells in dose-time dependent manner after treated by 20-250μmol/ L mangiferin for 24、48 hours.③Mangiferin efficiently suppressed the expression of FAK、CXCR4 and MMP-2 mRNA in HL-60 cells, the expression of FAK mRNA in dose-time dependent manner. The expression of CXCR4 and MMP-2 mRNA not statistical significance after treament with mangiferin for 24 hours exposure of HL-60 cells from 20μmol/L. It efficiently suppressed from 40μmol/L and the proportion of which with 160μmol/L and 200μmol/L mangiferin was significantly lower than that occurring in untreated cells. It’s not statistical significance that expression of CXCR4 and MMP-2 genes treated with mangiferin for 48 hours and high concentration but it’s statistical significance compare with that occurring in untreated cells. (P<0.05).
Conclusion Mangiferin can inhibits obviously the invasive ability of leukemia HL-60 cells and its mechanism may be related to inhibit obviously the capability of adhesion and reduce the expression of FAK CXCR4 and MMP-2 mRNA.
引文
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3.Aznavoorian S,Stetler-Stevenson WG and Liotta LA. Molecular aspects of tumor cell invasion and metastasis[J].Cancer,1993,71(4):1368-1383.
4.Konh EC and Liotta LA.Molecular insights into cancer invasion: strategies for prevention and intervention[J].Cancer Res,1995,55(9):1856-1862.
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6.MohLe R,Buatz F,Rafii S,etc.The ehemokine recptor CXCR-4 is expressed On CD34+ hematopoietic porgenitors and leukemic cells and mediates trans- endothelial migration induced by stromal cell-derived fctor-1[J].Blood,1998 91(12):4523-4530.
7.BugrerJA,KippsTJ.Chmeokine receptors and stromal cells in the homing and homeostasis of chronic lymphocytic leukemia B cells[J].Leuk Lymphoma, 2002,43(3):461-466.
8.Dunussi-Joannopoulos K,Zuberek K,Runyon K,etc. Efficacious immun- omodulatory activity of the chemokine stromal cell-derived factor l (SDF -l):local secretion of SDF-1 at the tumor site sevres as T-cell chemoattractant and mediates T-cell-dependent antitumor responses[J].Blood,2002,100(5): 1551-1558.
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