氧化铁纳米颗粒通过诱导巨噬细胞释放活性氧抑制膀胱癌的研究
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摘要
目的:研究氧化铁纳米颗粒(ION)通过诱导巨噬细胞产生活性氧(ROS)进而抑制膀胱癌的作用,探讨ION作为膀胱灌注新型药物制剂的可能性。方法:体外培养小鼠膀胱癌细胞MB49,利用ROS试剂盒检测其与小鼠巨噬细胞RAW264. 7、ION不同情况下共培养时ROS含量。利用CCK-8、Calcein-AM/PI染色检测MB49与RAW264. 7、ION不同条件下共培养的细胞活性与死亡情况。体内建立小鼠原位膀胱癌细胞种植模型,观测ION对膀胱肿瘤种植能力的影响。建立小鼠皮下瘤模型,瘤内注射ION后,监测肿瘤大小。结果:体外实验:RAW264. 7和ION可以产生ROS,并且可以被去铁胺(DFO)抑制,MB49与RAW264. 7和ION共同培养时细胞活性最低并且肿瘤死亡程度最高(P <0. 05)。体内试验:ION可以阻止膀胱癌细胞种植于膀胱壁,并且抑制膀胱癌的生长。结论:ION可以通过诱导巨噬细胞产生ROS抑制膀胱癌细胞的种植与生长,有望成为新型膀胱灌注药物。
Objective: To investigate the effect that iron oxide nanoparticles(ION) inhibit bladder cancer by inducing macrophage producing reactive oxygen species(ROS),and discuss its potential of intravesical treatment for bladder cancer. Methods: Mouse bladder cancer cell MB49 was cultured in vitro. ROS was evaluated when MB49 was co-cultured with RAW264. 7 and ION in different situations. CCK-8 assay and Calcein-AM/PI staining were used to assess cell viability and death of MB49. Cell implantation model was established in vivo. We observed whether the ability of MB49 implanting into the bladder wall was decreased. Subcutaneous transplantation tumor model was established and tumor size were assessed to detect whether intratumor injection of ION could inhibit bladder cancer. Results: In vitro study,RAW264. 7 could produce ROS when cultured with ION,but ROS reduced when DFO was added. When cocultured with RAW264. 7 and ION,the ability of MB49 proliferation was lowest and death was highest(P < 0. 05). In vivo study,tumor formation rate and tumor size were reduced when MB49 was treated with ION. Conclusion: ION can inhibit bladder cancer by inducing macrophage producing ROS and may be potential of intravesical treatment for bladder cancer.
Objective: To investigate the effect that iron oxide nanoparticles(ION) inhibit bladder cancer by inducing macrophage producing reactive oxygen species(ROS),and discuss its potential of intravesical treatment for bladder cancer. Methods: Mouse bladder cancer cell MB49 was cultured in vitro. ROS was evaluated when MB49 was co-cultured with RAW264. 7 and ION in different situations. CCK-8 assay and Calcein-AM/PI staining were used to assess cell viability and death of MB49. Cell implantation model was established in vivo. We observed whether the ability of MB49 implanting into the bladder wall was decreased. Subcutaneous transplantation tumor model was established and tumor size were assessed to detect whether intratumor injection of ION could inhibit bladder cancer. Results: In vitro study,RAW264. 7 could produce ROS when cultured with ION,but ROS reduced when DFO was added. When cocultured with RAW264. 7 and ION,the ability of MB49 proliferation was lowest and death was highest(P < 0. 05). In vivo study,tumor formation rate and tumor size were reduced when MB49 was treated with ION. Conclusion: ION can inhibit bladder cancer by inducing macrophage producing ROS and may be potential of intravesical treatment for bladder cancer.
引文
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[5]Sylvester RJ,Oosterlinck W,Holmang S,et al.Systematic review and individual patient data meta-analysis of randomized trials comparing a single immediate instillation of chemotherapy after transurethral resection with transurethral resection alone in patients with stage p Ta-pT1 urothelial carcinoma of the bladder:which patients benefit from the instillation?[J].Eur Urol,2016,69:231-244.
[6]Voltaggio L,Cimino Mathews A,Bishop JA,et al.Current concepts in the diagnosis and pathobiology of intraepithelial neoplasia:A review by organ system[J].Ca-Cancer J Clin,2016,66(5):408-436.
[7]Farr SE,Chess-Williams R,Mcdermott CM.Gemcitabine:Selective cytotoxicity,induction of inflammation and effects on urothelial function[J].Toxicol Appl Pharm,2017,316:1-9.
[8]Conde J,Oliva N,Zhang Y,et al.Local triple-combination therapy results in tumour regression and prevents recurrence in a colon cancer model[J].Nat Mater,2016,15(10):1128.
[9]Lin T,Yuan A,Zhao X,et al.Self-assembled tumor-targeting hyaluronic acid nanoparticles for photothermal ablation in orthotopic bladder cancer[J].Acta Biomater,2017,53:427.
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