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Dihydroartemisinin down-regulates the expression of transferrin receptor in myeloid leukemia cells
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- Author:
- No author available
- Journal Title:
- ACTA PHARMACEUTICA SINICA
- Issue:
- 6
- DOI:
- 10.3321/j.issn:0513-4870.2008.06.005
- Key Word:
- 二氢青蒿素;转铁蛋白受体;K562细胞;HL60细胞;铁饱和转铁蛋白
Abstract： 通过建立常铁HL60和K562细胞以及富铁K562细胞体外模型,研究二氢青蒿素对粒系白血病细胞转铁蛋白受体(transferrin receptor,TfR)的调控作用.采用流式细胞术检测二氢青蒿素对粒系白血病细胞TfR密度的调控作用,Western blotting和RT-PCR法检测二氢青蒿素对粒系白血病细胞TfR表达的调控作用,原子吸收分光光度法检测二氢青蒿素对常铁和富铁K562细胞铁含量的影响,以及MTT法和台盼蓝拒染法分析二氢青蒿素对粒系白血病细胞增殖的作用.结果显示,二氢青蒿素能显著降低常铁HL60和K562细胞TfR的密度和下调TfR蛋白的表达,且呈浓度和时间依赖性,并能有效地抑制细胞增殖,IC50值分别为1.74和11.33 μmol*L-1.二氢青蒿素对富铁K562细胞的TfR蛋白和mRNA表达能进一步增强下调作用,与常铁培养组比较,10 μmol*L-1二氢青蒿素对富铁K562细胞TfR蛋白和TfR mRNA表达量分别下调了28.1%(P<0.01)和26.2%(P<0.05),并能显著下降富铁K562细胞铁的含量(P<0.05),更有效地抑制富铁K562细胞增殖.由此可见,二氢青蒿素能下调粒系白血病细胞TfR密度以及TfR蛋白和mRNA的表达,有效抑制常铁HL60和K562细胞的增殖,对富铁K562细胞增殖的抑制作用能进一步增强.
- [1]李傲,周慧君.二氢青蒿素诱导HL-60细胞凋亡[J].2007,(3).
- [2]I S, Trowbridge,D L, Domingo.Anti-transferrin receptor monoclonal antibody and toxin-antibody conjugates affect growth of human tumour cells.[J].1981,294.
- [3]Maggs JL,Cohen GM,O'Neill PM,etc.Evidence for the involvement of carbon-centered radicals in the induction of apoptotic cell death by artemisinin compounds.[J].2007,282(13).
- [4]Kim MS,Lee SH,Lee CH,etc.Dihydroartemisinin enhances radiosensitivity of human glioma cells in vitro.[J].2006,132(2).
- [5]D L, Domingo,I S, Trowbridge.Transferrin receptor as a target for antibody-drug conjugates.[J].1985,112.
- [6]Moore J.Oral administration of dihydroartemisinin and ferrous sulfate retarded implanted fibrosarcoma growth in the rat[J].1995.
- [7]Chen HH,Zhou HJ,Fang X.Inhibition of human cancer cell line growth and human umbilical vein endothelial cell angiogenesis by artemisinin derivatives in vitro.[J].2003,48(3).
- [8]Sasaki T,Singh NP,Lai H.Targeted treatment of cancer with artemisinin and artemisinin-tagged iron-carrying compounds.[J].2005,9(5).
- [9]H N, Keer,J M, Kozlowski,Y C, Tsai,etc.Elevated transferrin receptor content in human prostate cancer cell lines assessed in vitro and in vivo.[J].1990,143.
- [10]Dela Cruz JS,Stinebaugh JM,Ng PP,etc.An anti-transferrin receptor-avidin fusion protein exhibits both strong proapoptotic activity and the ability to deliver various molecules into cancer cells.[J].2002,99(16).
- [11]Head JF,Yang DC,Wang F,etc.Expression of transferrin receptor and ferritin H-chain mRNA are associated with clinical and histopathological prognostic indicators in breast cancer.[J].2001,21(1B).
- [12]屠呦呦.The Development of New Antimalarial Drugs: Qinghaosu and Dihydroqinghaosu[J].1999,(11).
- [13]Daniels TR,Delgado T,Rodriguez JA,etc.The transferrin receptor part I: Biology and targeting with cytotoxic antibodies for the treatment of cancer.[J].2006,121(2).
- [14]Efferth T,Olbrich A,Bauer R.mRNA expression profiles for the response of human tumor cell lines to the antimalarial drugs artesunate, arteether, and artemether.[J].2002,64(4).
- [15]J M Lloyd,T O'Dowd,M Driver,etc.Demonstration of an epitope of the transferrin receptor in human cervical epithelium--a potentially useful cell marker.[J].1984,37(2).
- [16]R, Taetle.The role of transferrin receptors in hemopoietic cell growth.[J].1990,18.
- [17]Sauerbrey A,Miyachi H,Efferth T,etc.The anti-malarial artesunate is also active against cancer.[J].2001,18(4).