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BALB/c裸鼠浸润性膀胱癌模型的构建及通过髂内动脉灌注白蛋白结合型三氧化二砷(As2O3)治疗膀胱肿瘤的初步研究

Construction of a BALB/c-Nu Mouse Model of Invasive Bladder Carcinoma and Preliminary Studies on the Treatment of Bladder Tumors through Internal Iliac Arterial Infusion of Albumin-Bound Arsenic Trioxide (As2O3).

作者信息

Li Yunlong, Yu Guopeng, Li Qiaoxing, Wang Weilu, Shen Xiangqian, Liu Hua, Liu Ruijiang

机构信息

Department of Urology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, Suzhou 215300, P.R. China.

Department of Urology, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China; Fudan Institute of Urology, Fudan University, Shanghai 200040, P.R. China.

出版信息

PLoS One. 2015 Apr 27;10(4):e0124959. doi: 10.1371/journal.pone.0124959. eCollection 2015.

Abstract

To establish a BALB/c-nu mouse model of invasive bladder carcinoma and to investigate the feasibility, efficacy, and side effects of treating the mouse xenografts with internal iliac arterial infusion of albumin-bound arsenic trioxide (As2O3). Bladder tumors were established by intravesicular injection. Color Doppler were used to monitor tumor growth. Albumin-bound As2O3 and bovine serum albumin (BSA) nanoparticles were synthesized by cross-linking. BALB/c-nu mice were randomly divided into four treatment groups: 1) normal saline, 2) BSA nanoparticles, 3) As2O3 injections, and 4) albumin-bound As2O3. In an attempt to replicate the treatment of bladder cancer in humans using internal iliac arterial infusion, the drugs were injected into the mouse abdominal aorta. Tumor xenografts were established successfully. Mice treated with As2O3 injections and with albumin-bound As2O3 had significantly smaller bladders (36.59% and 37.82% smaller, respectively) than mice given normal saline injections (P < 0.01). Mice receiving As2O3 injections had lower white blood cell (WBC) and platelet counts compared with mice receiving normal saline injections only (P < 0.05). However, mice treated with albumin-bound As2O3 did not experience a significant decrease in WBC or platelet counts compared with control mice. A model of intra-arterial bladder cancer treatment was successfully established in BALB/c-nu mice. In this model, albumin-bound As2O3 appeared to be an effective method for treating bladder tumors, with less severe hematologic side effects compared with As2O3 alone. The infusion of albumin-bound As2O3 through the internal iliac artery is a promising method of bladder cancer therapy.

摘要

建立BALB/c-nu小鼠浸润性膀胱癌模型,并研究经髂内动脉灌注结合白蛋白的三氧化二砷(As2O3)治疗小鼠异种移植瘤的可行性、疗效及副作用。通过膀胱内注射建立膀胱肿瘤。使用彩色多普勒监测肿瘤生长。通过交联合成结合白蛋白的As2O3和牛血清白蛋白(BSA)纳米颗粒。将BALB/c-nu小鼠随机分为四个治疗组:1)生理盐水组,2)BSA纳米颗粒组,3)As2O3注射组,4)结合白蛋白的As2O3组。为尝试复制人类使用髂内动脉灌注治疗膀胱癌的方法,将药物注入小鼠腹主动脉。成功建立肿瘤异种移植模型。与注射生理盐水的小鼠相比,接受As2O3注射和结合白蛋白的As2O3治疗的小鼠膀胱明显更小(分别小36.59%和37.82%)(P<0.01)。与仅接受生理盐水注射的小鼠相比,接受As2O3注射的小鼠白细胞(WBC)和血小板计数较低(P<0.05)。然而,与对照小鼠相比,接受结合白蛋白的As2O3治疗的小鼠WBC或血小板计数没有显著下降。在BALB/c-nu小鼠中成功建立了动脉内膀胱癌治疗模型。在该模型中,结合白蛋白的As2O3似乎是治疗膀胱肿瘤的有效方法,与单独使用As2O3相比,血液学副作用较轻。通过髂内动脉灌注结合白蛋白的As2O3是一种有前景的膀胱癌治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb4d/4410949/1cbdb17cd74f/pone.0124959.g001.jpg

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