昆明小鼠和DBA/2小鼠尾静脉注射L1210细胞的比较研究
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摘要
目的:通过尾静脉注射L1210细胞建立昆明小鼠及DBA/2小鼠的白血病模型,观察肿瘤细胞的迁移情况以及小鼠存活时间,为后续L1210细胞迁移的细胞内信号通路研究及抗肿瘤药物筛选奠定基础。方法:常规培养小鼠白血病细胞L1210系,将昆明小鼠及DBA/2小鼠随机分为对照组(A、C)和实验组(B、D),实验组尾静脉注射5×106L1210细胞,对照组注射等体积的PBS。昆明小鼠组饲养56 d,DBA/2小鼠组饲养14 d。定期测量小鼠体重并观察小鼠形态,取濒死小鼠以及最后解剖的小鼠的心、肝、脾、肺等脏器称重并测量,统计结果。结果:A、B、C、D组小鼠的平均存活天数分别为56、56、13.83±0.37、10.33±3.40 d。昆明小鼠实验组脾脏明显肿大,肺脏有少量白细胞浸润,心脏和肝脏无明显变化,无死亡现象;DBA/2小鼠注射L1210细胞后第7 d开始出现死亡,随着饲养时间的延长,死亡率不断上升。结论:昆明小鼠或DBA/2小鼠尾静脉注射L1210细胞均可引起肿瘤细胞的体内浸润。昆明小鼠尾静脉注射L1210细胞存活时间长,适合长期观察或周期比较长的实验;DBA/2小鼠尾静脉注射L1210细胞存活时间短,但实验现象明显。后期研究可以针对不同的研究目的和实验周期来选择合适的实验模型。
Objective: The leukemia model of Kunming mice and DBA/2 mice was established by injecting L1210 cells into the tail vein, the migration tumor cells and survival time of mices were observed, which will laid a foundation for the study of intracellular signaling pathways of subsequent L1210 cell migration and screening of antitumor drugs. Methods: The mouse leukemia cell line L1210 was routinely cultured, and Kunming mice and DBA/2 mice were randomly divided into control group(A, C) and experimental group(B, D). The experimental group was treated with 5×106 L1210 cells in the tail vein. The control group was injected with an equal volume of PBS. Kunming mice were fed for 56 days and DBA/2 mice were fed for 14 days. The body weight of the mice was measured regularly and the morphology of the mice was observed. The hearts, liver, spleen, lungs and other organs of the dead mice and the dissected mice were weighed and measured, and the results were statistically analyzed. Results: The average survival days of the four groups A, B, C, and D were 56, 56, 13.83±0.37, 10.33±3.40 d, respectively. There was no death in the Kunming mouse experimental group, the spleen was swollen, and there was a small amount of leukocyte infiltration in the lungs. There was no significant change in the heart and liver. The DBA/2 mice injected with L1210 cells began to die on the seventh day, and the mortality rate increased with the increase of feeding time. Conclusion: Injecting L1210 cells into the tail vein of Kunming mice or DBA/2 mice can cause in vivo infiltration of tumor cells. The L1210 cells injected into the tail vein of Kunming mice have a long survival time and are suitable for long-term observation or long-term experiments. The survival time of L1210 cells injected into the tail vein of DBA/2 mice was short, but the experimental phenomenon was obvious. We can select appropriate experimental models for different research purposes and experimental cycles in later studies.
Objective: The leukemia model of Kunming mice and DBA/2 mice was established by injecting L1210 cells into the tail vein, the migration tumor cells and survival time of mices were observed, which will laid a foundation for the study of intracellular signaling pathways of subsequent L1210 cell migration and screening of antitumor drugs. Methods: The mouse leukemia cell line L1210 was routinely cultured, and Kunming mice and DBA/2 mice were randomly divided into control group(A, C) and experimental group(B, D). The experimental group was treated with 5×106 L1210 cells in the tail vein. The control group was injected with an equal volume of PBS. Kunming mice were fed for 56 days and DBA/2 mice were fed for 14 days. The body weight of the mice was measured regularly and the morphology of the mice was observed. The hearts, liver, spleen, lungs and other organs of the dead mice and the dissected mice were weighed and measured, and the results were statistically analyzed. Results: The average survival days of the four groups A, B, C, and D were 56, 56, 13.83±0.37, 10.33±3.40 d, respectively. There was no death in the Kunming mouse experimental group, the spleen was swollen, and there was a small amount of leukocyte infiltration in the lungs. There was no significant change in the heart and liver. The DBA/2 mice injected with L1210 cells began to die on the seventh day, and the mortality rate increased with the increase of feeding time. Conclusion: Injecting L1210 cells into the tail vein of Kunming mice or DBA/2 mice can cause in vivo infiltration of tumor cells. The L1210 cells injected into the tail vein of Kunming mice have a long survival time and are suitable for long-term observation or long-term experiments. The survival time of L1210 cells injected into the tail vein of DBA/2 mice was short, but the experimental phenomenon was obvious. We can select appropriate experimental models for different research purposes and experimental cycles in later studies.
引文
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[14]焦丽,陈彩平,李林瑞,等.不同方法接种构建的可移植性小鼠L1210白血病模型的生物学特性[J].武警医学,2011,22(3):208-211.
[15]Sirotnak F M,Moccio D M,Dorick D M.Optimization of high-dose methotrexate with leucovorin rescue therapy in the L1210 leukemia and sarcoma 180 murine tumor models[J].Cancer Res,1978,38(2):345-353.
[16]Canti G,Franco P,Marelli O,et al.Hematoporphyrin derivative rescue from toxicity caused by chemotherapy or radiation in a murine leukemia model(L1210)[J].Cancer Res,1980,44(4):1551-1556.
[17]Aldred A J,Cha M C,Meckling-Gill K A.Determination of a humane endpoint in the L1210 model of murine leukemia[J].Contemp Top Lab Anim Sci,2002,41(2):24-27.
[18]Kozar K,Kamiński R,Switaj T,et al.Interleukin 12-based immunotherapy improves the antitumor effectiveness of a low-dose 5-Aza-2'-deoxycitidine treatment in L1210 leukemia and B16F10 melanoma models in mice[J].Clin Cancer Res,2003,9(8):3124.
[19]Pan X Q,Lee R J.In vivo antitumor activity of folate receptor-targeted liposomal daunorubicin in a murine leukemia model[J].Anticancer Res,2005,25:343-346.
[20]刘秋燕,吕占军.L1210克隆细胞肿瘤动物模型生物学特性研究[J].中国实验动物学报,2002,10(1):47-50.
[21]李覃,王伟,李彤.白藜芦醇体外及小鼠体内抗白血病作用机制[J].中西医结合学报,2008,6(12):1267-1274.
[22]Jackson H,Jackson N C,Bock M,et al.Testicular relapse in acute lymphoblastic leukaemia:studies with an experimental mouse model[J].Br J Cancer,1984,49(1):73.
[23]田晓琳,许亚梅,王珍珍,等.尾静脉注射及皮下接种方法建立小鼠高表达miR-17-92的L1210白血病模型的比较研究[J].中华临床医师杂志(电子版),2013,7(8):3449-3453.
[2]Morton D B.Advances in refinement in animal experimentation over past 25 years[J].Altern Lab Anim,1995,23(6):812-822.
[3]司富春,王振旭.白血病中医证型与方药分析[J].中华中医药杂志,2013,(7):1971-1976.
[4]She M,Niu X,Chen X,et al.Resistance of leukemic stem-like cells in AML cell line KG1a to natural killer cell-mediated cytotoxicity[J].Cancer Lett,2012,318(2):173-179.
[5]Saito Y,Kitamura H,Hijikata A,et al.Identification of therapeutic targets for quiescent,chemotherapy-resistant human leukemia stem cells[J].Sci Transl Med,2010,2(17):17ra9.
[6]Macgrath S M,Koleske A J.Cortactin in cell migration and cancer at a glance[J].J Cell Sci,2012,125(7):1621-1626.
[7]Chodniewicz D,Klemke R L.Guiding cell migration through directed extension and stabilization of pseudopodia[J].Exp Cell Res,2004,301(1):31-37.
[8]贾晋松,哈森,苏秀兰,等.白血病心脏浸润所致心肌凋亡研究[J].心脏杂志,2001,13(6):459-460.
[9]Williamc R S,Bodey G P,Wertlake P T.The heart in acute leukemia[J].Am J Cardiol,1968,21(3):388-412.
[10]葛林阜,曹雪涛,马大烈,等.白细胞介素6基因转染的白血病细胞体内抗白血病浸润的病理形态研究[J].中华肿瘤杂志,1995,(6):409-411.
[11]王怀禄,王瑜琴,刘俊娥.白血病多脏器浸润1例[J].中国临床医学影像杂志,2005,16(6):360-360.
[12]李云,刘胜全,闫呈新.白血病肺浸润的CT表现[J].中国CT和MRI杂志,2009,7(4):12-14.
[13]何宏星,吴正财,张望平,等.不同接种方法建立小鼠L1210白血病模型的比较研究[J].实验动物与比较医学,2007,27(2):112-115.
[14]焦丽,陈彩平,李林瑞,等.不同方法接种构建的可移植性小鼠L1210白血病模型的生物学特性[J].武警医学,2011,22(3):208-211.
[15]Sirotnak F M,Moccio D M,Dorick D M.Optimization of high-dose methotrexate with leucovorin rescue therapy in the L1210 leukemia and sarcoma 180 murine tumor models[J].Cancer Res,1978,38(2):345-353.
[16]Canti G,Franco P,Marelli O,et al.Hematoporphyrin derivative rescue from toxicity caused by chemotherapy or radiation in a murine leukemia model(L1210)[J].Cancer Res,1980,44(4):1551-1556.
[17]Aldred A J,Cha M C,Meckling-Gill K A.Determination of a humane endpoint in the L1210 model of murine leukemia[J].Contemp Top Lab Anim Sci,2002,41(2):24-27.
[18]Kozar K,Kamiński R,Switaj T,et al.Interleukin 12-based immunotherapy improves the antitumor effectiveness of a low-dose 5-Aza-2'-deoxycitidine treatment in L1210 leukemia and B16F10 melanoma models in mice[J].Clin Cancer Res,2003,9(8):3124.
[19]Pan X Q,Lee R J.In vivo antitumor activity of folate receptor-targeted liposomal daunorubicin in a murine leukemia model[J].Anticancer Res,2005,25:343-346.
[20]刘秋燕,吕占军.L1210克隆细胞肿瘤动物模型生物学特性研究[J].中国实验动物学报,2002,10(1):47-50.
[21]李覃,王伟,李彤.白藜芦醇体外及小鼠体内抗白血病作用机制[J].中西医结合学报,2008,6(12):1267-1274.
[22]Jackson H,Jackson N C,Bock M,et al.Testicular relapse in acute lymphoblastic leukaemia:studies with an experimental mouse model[J].Br J Cancer,1984,49(1):73.
[23]田晓琳,许亚梅,王珍珍,等.尾静脉注射及皮下接种方法建立小鼠高表达miR-17-92的L1210白血病模型的比较研究[J].中华临床医师杂志(电子版),2013,7(8):3449-3453.
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