补充硫胺素可减轻 Wilson 病 Atp7b 小鼠模型中的肝细胞癌。
Thiamine supplementation attenuated hepatocellular carcinoma in the Atp7b mouse model of Wilson's disease.
机构信息
Department of Ophthalmology and the Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite D, New Orleans, LA 70112, U.S.A.
出版信息
Anticancer Res. 2011 Oct;31(10):3395-9.
BACKGROUND
Wilson's disease is caused by a genetic defect in P-type Cu(2+)-ATPase (Atp7b), resulting in Cu(2+) accumulation in the liver, toxicity, and hepatocellular carcinoma. Exposure of HepG2 cells, and livers of Atp7b mutant mice to toxic Cu(2+) resulted in oxidation, (KGDH) and (PDH) enzyme inhibition, and death that was attenuated by thiamine.
MATERIALS AND METHODS
The effect of oral thiamine supplementation (2%) on hepatocellular carcinoma induced by Cu(2+) accumulation in the livers of Atp7b animals at 4, 6, 9, 12, 16, and 21 months was demonstrated using gross morphology and multi-nucleate analysis.
RESULTS
By 16 months of age, untreated Atp7b animals became moribund, their livers were >180% the weight of controls and >75% of their liver was cancerous. At 16 months the livers of thiamine treated Atp7b mice were <130% the weight of controls and <30% cancerous, and at 21 months the mice were still active. However thiamine was ineffective in a subcutaneous xenograft model.
CONCLUSION
This study suggests that thiamine may constitute a prophylactic for Wilson's disease-induced hepatocellular carcinoma.
背景
威尔逊病是由 P 型铜（2+）-ATP 酶（Atp7b）的遗传缺陷引起的，导致铜（2+）在肝脏中积累、毒性和肝细胞癌。将 HepG2 细胞和 Atp7b 突变小鼠的肝脏暴露于有毒的 Cu（2+）中会导致氧化、（KGDH）和（PDH）酶抑制以及死亡，而硫胺素可减轻这种死亡。
材料和方法
通过肉眼观察和多核分析，证明了口服硫胺素补充（2%）对 Atp7b 动物肝脏中 Cu（2+）积累诱导的肝细胞癌的影响，实验时间为 4、6、9、12、16 和 21 个月。
结果
未经治疗的 Atp7b 动物在 16 个月大时濒死，其肝脏重量是对照组的 180%以上，且 75%以上的肝脏发生癌变。在 16 个月时，接受硫胺素治疗的 Atp7b 小鼠的肝脏重量不到对照组的 130%，癌变不到 30%，且在 21 个月时，这些小鼠仍然活跃。然而，硫胺素在皮下异种移植模型中无效。
结论
本研究表明，硫胺素可能构成威尔逊病诱导的肝细胞癌的预防性治疗方法。
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