原子力显微镜研究多西他赛对人肺腺癌A549细胞的作用机制
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摘要
利用原子力显微镜(AFM)研究了化疗药物多西他赛对肺腺癌细胞A549的作用机制。选取了不同浓度多西他赛作用下的A549细胞,观察和分析了多西他赛对A549细胞形貌信息和生物力学特性的影响。结果表明细胞的峰谷差和超微结构的平均粗糙度随着药物浓度增加而减小,表面粘附力随着药物浓度增加而增大。该结果对AFM可作为一种利用纳米量级分辨率进行药物药效评估的工具进行了佐证。
The mechanics of docetaxel on lung cancer cells of A549 has been studied by atomic force microcopy( AFM). Different cells of A549 affected by the different concentrations of docetaxel were used. The analysis showed that docetaxel can affect the morphological information and biomechanical properties. The results showed that the value of valley-to-peak and average roughness decrease,and adhesive force of cell surface increases when the concentration of docetaxel increases. The AFM may potentially be developed into a tool in evaluating drug effect at nanometer scale is supported.
The mechanics of docetaxel on lung cancer cells of A549 has been studied by atomic force microcopy( AFM). Different cells of A549 affected by the different concentrations of docetaxel were used. The analysis showed that docetaxel can affect the morphological information and biomechanical properties. The results showed that the value of valley-to-peak and average roughness decrease,and adhesive force of cell surface increases when the concentration of docetaxel increases. The AFM may potentially be developed into a tool in evaluating drug effect at nanometer scale is supported.
引文
[1]FOLKMAN J.Tumor angiogenesis:therapeutic implications[J].N Engl J Med,1971,285(21):1182-1186.
[2]O'REILLY M S,BOEHM T,SHING Y,et al.Endostatin:an endogenous inhibitor of angiogenesis and tumor growth[J].Cell,1997,88(2):277-285.
[3]WANG J,SUN Y,LIU Y,et al.Results of randomized,multicenter,double-blind phase III trial of rh-endostatin(YH-16)in treatment of advanced non-small cell lung cancer patients[J].Zhongguo Fei Ai Za Zhi,2005,8(4):283-290.
[4]SASAKI T,FUKAI N,NANN K,et al.Structure,unction and tissue forms of the C-terminal globuarolomain of collagen XVIII contmning the angio-genesisinhibitor endostatin[J].EMBO J,1998,17(15):4249-4256.
[5]RAMASWAMY B,ELIAS A D,KELBICK N T,et al.Phase II trial of bevacizumab in combination with weekly docetaxel in metastatic breast cancer patients[J].Clin Cancer Res,2006,12(10):3124-3129.
[6]GRANT D S,WILLIAMS T L,ZAHAZEWSKY M,et al.Comparison of antiangiogenic activities using paclitaxel(taxol)and docetaxel(taxotere)[J].Int J Cancer,2003,104(1):121-129.
[7]INOUE K,CHIKAZAWA M,FUKATA S,et al.Docetaxel enhances the therapeutic effect of the angiogenesis inhibitor TNP-470(AGM-1470)in metastatic human transitional cell carcinoma[J].Clin Cancer Res,2003,9(2):886-899.
[8]HOTCHKISS K A,ASHTON A W,MAHMOOD R,et al.Inhibition of endothelial cell function in vitro and angiogenesis in vivo by docetaxel(Taxotere):association with impaired repositioning of the microtubule organizing center[J].Mol Cancer Ther,2002,1(13):1191-1200.
[9]NAWROCKI S T,SWEENEY-GOTSCH B,TAKAMORI R,et al.The proteasome inhibitor bortezomib enhances the activity of docetaxel in orthotopic human pancreatic tumor xenografts[J].Mol Cancer Ther,2004,3(1):59-70.
[10]BINNIG G,QUATE C F,GERBER C.Atomic force microscope[J].Phys Rev Lett,1986,56(9):930-933.
[11]HRBER J K,MILES M J.Scanning probe evolution in biology[J].Science,2003,302(5647):1002-1013.
[12]HINTERDORFER P,DUFRNE Y F.Detection and localization of single molecular recognition events using atomic force microscopy[J].Nat Meth,2006,3:347-355.
[13]WILLEMSEN O H,SNEL M M,CAMBI A,et al.Biomolecular interactions measured by atomic force microscopy[J].Biophys J,2000,79(6):3267-3281.
[14]KIENBERGER F,EBNER A,GRUBER H J,et al.Molecular recognition imaging and force spectroscopy of single biomolecules[J].Acc Chem Res,2006,39(1):29-36.
[15]FOTIADIS D,SCHEURING S,MLLER S A,et al.Imaging and manipulation of biological structures with the AFM[J].Micron,2002,33(4):385-397.
[2]O'REILLY M S,BOEHM T,SHING Y,et al.Endostatin:an endogenous inhibitor of angiogenesis and tumor growth[J].Cell,1997,88(2):277-285.
[3]WANG J,SUN Y,LIU Y,et al.Results of randomized,multicenter,double-blind phase III trial of rh-endostatin(YH-16)in treatment of advanced non-small cell lung cancer patients[J].Zhongguo Fei Ai Za Zhi,2005,8(4):283-290.
[4]SASAKI T,FUKAI N,NANN K,et al.Structure,unction and tissue forms of the C-terminal globuarolomain of collagen XVIII contmning the angio-genesisinhibitor endostatin[J].EMBO J,1998,17(15):4249-4256.
[5]RAMASWAMY B,ELIAS A D,KELBICK N T,et al.Phase II trial of bevacizumab in combination with weekly docetaxel in metastatic breast cancer patients[J].Clin Cancer Res,2006,12(10):3124-3129.
[6]GRANT D S,WILLIAMS T L,ZAHAZEWSKY M,et al.Comparison of antiangiogenic activities using paclitaxel(taxol)and docetaxel(taxotere)[J].Int J Cancer,2003,104(1):121-129.
[7]INOUE K,CHIKAZAWA M,FUKATA S,et al.Docetaxel enhances the therapeutic effect of the angiogenesis inhibitor TNP-470(AGM-1470)in metastatic human transitional cell carcinoma[J].Clin Cancer Res,2003,9(2):886-899.
[8]HOTCHKISS K A,ASHTON A W,MAHMOOD R,et al.Inhibition of endothelial cell function in vitro and angiogenesis in vivo by docetaxel(Taxotere):association with impaired repositioning of the microtubule organizing center[J].Mol Cancer Ther,2002,1(13):1191-1200.
[9]NAWROCKI S T,SWEENEY-GOTSCH B,TAKAMORI R,et al.The proteasome inhibitor bortezomib enhances the activity of docetaxel in orthotopic human pancreatic tumor xenografts[J].Mol Cancer Ther,2004,3(1):59-70.
[10]BINNIG G,QUATE C F,GERBER C.Atomic force microscope[J].Phys Rev Lett,1986,56(9):930-933.
[11]HRBER J K,MILES M J.Scanning probe evolution in biology[J].Science,2003,302(5647):1002-1013.
[12]HINTERDORFER P,DUFRNE Y F.Detection and localization of single molecular recognition events using atomic force microscopy[J].Nat Meth,2006,3:347-355.
[13]WILLEMSEN O H,SNEL M M,CAMBI A,et al.Biomolecular interactions measured by atomic force microscopy[J].Biophys J,2000,79(6):3267-3281.
[14]KIENBERGER F,EBNER A,GRUBER H J,et al.Molecular recognition imaging and force spectroscopy of single biomolecules[J].Acc Chem Res,2006,39(1):29-36.
[15]FOTIADIS D,SCHEURING S,MLLER S A,et al.Imaging and manipulation of biological structures with the AFM[J].Micron,2002,33(4):385-397.