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三氧化二砷对裸鼠宫颈癌移植瘤的作用及机制

Effects and Mechanism of Arsenic Trioxide on Growth of Cervical Cancer in Nude Mice

  • 摘要: 目的研究三氧化二砷 (arsenic trioxide,ATO,As2O3)对宫颈癌HeLa细胞裸鼠移植瘤生长的作用及机制。方法建立裸鼠移植瘤模型,分为低浓度As2O3组[2mg/(kg·d)],高浓度As2O3组[5mg/(kg·d)],顺铂(DDP)组[3mg/(kg·d)]及阴性对照组(0.9%氯化钠0.2ml/d),连续给药10d,观察抑瘤率及药物对裸鼠的影响。透射电子显微镜观察肿瘤的超微结构,免疫组织化学检测p-P38和Caspase-3的表达。结果低浓度As2O3,高浓度As2O3 及DDP的抑瘤率分别为22.95%、54.86%和54.48%,后两者的抑瘤率与阴性对照组的差异有统计学意义(P<0.05),但DDP的不良反应大。p-P38和Caspase-3在As2O3组的表达明显高于阴性对照组(P<0.05)。结论As2O3可通过诱导肿瘤细胞凋亡抑制宫颈癌移植瘤的生长。

     

    Abstract: ObjectiveTo explore the inhibitory effect of arsenic trioxide(ATO, As2O3) on the tumor growth of cervical cancer cell line HeLa subcutaneously implanted in nude mice and its mechanism. Methods Human cervical cancer xenografted model was established in nude mice.The tumor-bearing nude mice were randomly divided into the experimental groups: ATO low dose group [2mg/(kg·d)],ATO high dose group [5mg/(kg·d)],DDP positive control group [3mg/(kg·d)],saline negative control group(0.9%NaCl 0.2ml/d).The drugs were administered intraperitoneally for 10 consecutive days.To observe the tumor inhibition rate and effects of drugs.Ultramicrostructure feature of tumor was observed under electron microscope.Immunohistochemistry was used to measure the expression of p-P38 and Caspase-3. Results Inhibited tumor volume of ATO low and high dose groups and DDP positive control group was 22.95%,54.86% and 54.48%,respectively.The inhibited effect of ATO 5mg/kg/d group was similar with DDP 3mg/kg/d group, but the toxic effect of DDP was higher than ATO.The expression of p-P38 and Caspase-3 was higher than negative control group (P<0.05). Conclusion ATO can inhibit the growth of cervical cancer cells in vivo through enhancing apoptosis of tumor cells.

     

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