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| 磁性纳米Fe3O4颗粒协同化疗药物及5溴汉防己甲素在荷瘤鼠体内逆转耐药的研究 | |
| 引用本文： | 吴亚男,陈宝安,程坚,高峰,许文林,丁家华,高冲,孙新臣,李国宏,陈文姬,刘莉洁,李小毛,王雪梅.磁性纳米Fe3O4颗粒协同化疗药物及5溴汉防己甲素在荷瘤鼠体内逆转耐药的研究[J].中国实验血液学杂志,2009,17(1):60-64. |
| 作者姓名： | 吴亚男 陈宝安 程坚 高峰 许文林 丁家华 高冲 孙新臣 李国宏 陈文姬 刘莉洁 李小毛 王雪梅 |
| 作者单位： | 1. 东南大学中大医院血液科,江苏南京,210009 2. 江苏大学人民医院血液科,江苏,镇江,212002 3. 东南大学中大医院,肿瘤科,江苏南京,210009 4. 东南大学生理教研室,江苏南京,210009 5. 萨尔大学医学部,德国萨尔布吕肯D-66041 6. 东南大学生物电子学国家重点实验室,江苏南京,210096 |
| 基金项目： | 国家高技术研究发展计划(863计划)，国家自然科学基金，High School Doctor Subject Special-purpose Scientific Foundation |
| 摘 要： | 本研究探讨5溴汉防己甲素（5-BrTet）、磁性纳米Fe3O4（Fe3O4-MNP）协同化疗药在动物模型体内逆转耐药的作用及其作用机理。建立恶性血液病荷瘤鼠模型，将其随机分为5组。A组：生理盐水；B组：单用DNR；C组：5-BrTet复合DNR；D组：Fe3O4-MNPs复合DNR；E组：Fe3O4．MNPs复合DNR及5-BrTet。观察各组肿瘤生长特征，肿瘤重量、体积。取各组肿瘤以及心、肝、肾等脏器行组织病理观察。Western blot检测耐药肿瘤BCL-2，BAX，以及caspase-3表达。结果表明：对于K562移植瘤，B、C、D、E4个组之间肿瘤抑制率没有明显的差别。对于K562／A02移植瘤，Fe3O4-MNP复合DNR及5-BrTet可明显抑制移植瘤的增殖，促进肿瘤细胞凋亡；肿瘤组织病理观察显示肿瘤坏死明显。5-BrTet联合Fe3O4-MNP抑制K562／A02移植瘤的BCL-2蛋白的表达，下调BAX和caspas-3的表达。结论：在耐药肿瘤动物模型体内，Fe3O4-MNPs协同DNR和5-BrTet具有很强的肿瘤抑制作用。 |
| 关 键 词： | 5溴汉防己甲素 磁性纳米四氧化三铁颗粒 柔红霉素 多药耐药 移植瘤模型 白血病 |
Reversal of Multidrug Resistance in Xenograft Nude-mice by Magnetic Fe3O4 Nanoparticles Combined with Daunorubicin and 5-Bromotetrandrine |
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| WU Ya-Nan,CHEN Bao-An,CHENG Jian,GAO Feng,XU Wen-Lin,DING Jia-Hua,GAO Chong,SUN Xin-Chen,LI Guo-Hong,CHEN Wen-Ji,LIU Li-Jie,Li Xiao-Mao,WANG Xue-Mei.Reversal of Multidrug Resistance in Xenograft Nude-mice by Magnetic Fe3O4 Nanoparticles Combined with Daunorubicin and 5-Bromotetrandrine[J].Journal of Experimental Hematology,2009,17(1):60-64. | |
| Authors: | WU Ya-Nan CHEN Bao-An CHENG Jian GAO Feng XU Wen-Lin DING Jia-Hua GAO Chong SUN Xin-Chen LI Guo-Hong CHEN Wen-Ji LIU Li-Jie Li Xiao-Mao WANG Xue-Mei |
| Institution: | (Department of Hematology, Zhongda Hospital, Southeast University Clinical Medical School, Nanjing, 210009, Jiangsu Province, China ; 1.Department of Hematology, People Hospital, Jiangsu University, Zhenjiang 212002, Jiangsu Province, China ; 2. Department of Oncology, Zhongda Hospital, Southeast University Clinical Medical School, Nanjing 210009, Jiangsu Province, China ; 3.Department of Physiology, Southeast University, Nanjing 210009, Jiangsu Province, China ; 4.Department of Physics, University of Saarland , D-66041 Saarbruechen , Germany; 5.National Key Laboratory of Bioelectronics( Chien-Shiung Wu Laboratory), Southeast University, Nanjing 210096, Jiangsu Province, China) |
| Abstract: | This study was aimed to investigate the reversal effect of 5-bromotetrandrine(5-BrTet)and magnetic na noparticle of Fe3O4(Fe3O4-MNPs)combined with DNR in vivo.The xenograft leukemia model with stable multiple drug resistance in nude mice was established.The two sub clones of K562 and K562/A02 cells were respectively inocu 1ated subcutaneously into back of athymic nude mice(1×107 cells/each)to establish the leukemia xenografl models. Drug resistant and the sensitive tumor-bearing nude mice were both assigned randomly into 5 groups:group A was trea ted with NS:group B was treated with DNR;group C was treated with nanoparticle of Fe3O4 combined with DNR; group D was treated with 5-BrTet combined with DNR:group E was treated with 5-bromotetrandrine and magnetic nano particle of Fe3O4 combined with DNR.The incidence of tumor formation,growth characteristics,weight and volume of tumor were observed.The histopathologic examination of tumors and organs were carried out.The protein levels of BCL-2.BAX.and Caspase-3 in resistant tumors were detected by Western blot.The results indicated that 5-BrTet and magnetic nanoparticle of Fe3O4 combined with DNR significantly suppressed growth of K562/A02 cell xenogafi tumor, histopathologic examination of tumors showed the tumors necrosis obviously.Application of 5-BrTet and magnetic nano particle of Fe3O4 inhibited the expression of BCL-2 protein and up regulated the expression of BAX,and Caspase-3 pro tein in K562/A02 cell xenograft tumor.It is concluded that 5-bromotetrandrine and magnetic nanoparticle of Fe3O4 com bined wim DNR have significant tumor-suppressing effect on MDR leukemia cell xenograff model. |
| Keywords: | 5-bromotetrandrine magnetic nanoparticle of Fe3O4 daunorubicin multidrug-resistance xenograft model leukemia |
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