Turovsky Egor A, Gudkov Sergey V, Varlamova Elena G
Institute of Cell Biophysics of the Russian Academy of Sciences, Federal Research Center "Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences", 142290 Pushchino, Russia.
Prokhorov General Physics Institute of the Russian Academy of Sciences, 38 Vavilove st., 119991 Moscow, Russia.
Biomolecules. 2025 Sep 18;15(9):1336. doi: 10.3390/biom15091336.
Hepatocellular carcinoma is a primary malignant tumor of the liver, which is a serious health problem due to its aggressive nature, late diagnosis, and metastasis to other organs. We present, for the first time, the mRNA expression patterns of a wide range of genes involved in inflammation, fibrosis, endoplasmic reticulum stress, various forms of cell death, and signaling cascades in the lungs and kidneys of mice with thioacetamide-induced HCC. It is known that HCC often metastasizes to the lungs, and it is also important to understand which pathological processes occur in the kidneys, since the liver and kidneys are key target organs of toxicity. The main goal of this work was to study the pathological processes in the lungs and kidneys in HCC and the effectiveness of selenium nanocomplexes, as well as the well-known drug sorafenib, in mitigating these pathological consequences. These results present a significant contribution to the study of HCC metastasis to the lungs and kidneys and to the development of drugs that are most effective in the late stages of HCC. In addition, a hierarchy of the distribution of the selenium in the liver, kidneys, and lungs was established after the treatment of mice with HCC with selenium nanoparticles and a selenium-sorafenib nanocomplex. These data are important for developing a treatment protocol and determining optimal dosages of the drugs under study, which allows for achieving the desired therapeutic effect and neutralizing the toxic effect of selenium on healthy tissues and organs.
肝细胞癌是肝脏的原发性恶性肿瘤,由于其侵袭性、诊断延迟以及向其他器官转移,它是一个严重的健康问题。我们首次展示了硫代乙酰胺诱导的肝癌小鼠肺和肾中涉及炎症、纤维化、内质网应激、各种形式的细胞死亡以及信号级联反应的多种基因的mRNA表达模式。已知肝癌常转移至肺部,了解肾脏中发生哪些病理过程也很重要,因为肝脏和肾脏是毒性的关键靶器官。这项工作的主要目标是研究肝癌中肺和肾的病理过程以及硒纳米复合物和著名药物索拉非尼减轻这些病理后果的有效性。这些结果对肝癌转移至肺和肾的研究以及在肝癌晚期最有效的药物开发做出了重大贡献。此外,在用硒纳米颗粒和硒 - 索拉非尼纳米复合物治疗肝癌小鼠后,建立了硒在肝脏、肾脏和肺中的分布层次。这些数据对于制定治疗方案和确定所研究药物的最佳剂量很重要,这有助于实现预期的治疗效果并中和硒对健康组织和器官的毒性作用。