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CCR:王慧等发现剥夺铁离子可抑制肝癌

中科院上海生科院营养所、药物研究所,以及美国梅奥临床医学院等处的研究人员发现了抗癌小分子药物新型铁螯合剂TSC24(thiosemicarbazone-24)的作用新机制,这将为肝癌的预防和治疗提供新思路。这一研究成果发表在国际学术期刊Clinical Cancer Research上。

肝癌是严重影响人类健康的疾病,居世界肿瘤死因的第三位,开发以肝癌中异常高表达分子为靶点的高特异性抗癌药物具有重要的临床意义。铁是人体必需的微量元素之一,同时铁的过量蓄积是肝癌发生发展的重要危险因素之一,提示铁可以作为一种新的癌症治疗靶点。

营养所王慧组巴乾等研究人员在细胞及动物水平对新型铁螯合剂TSC24(thiosemicarbazone-24)的铁螯合效率和抗肝癌活性及其分子机理进行了深入探讨,发现TSC24可螯合铁、抑制铁吸收并打破细胞内铁的代谢平衡,造成细胞缺铁,同时诱导肝癌细胞G2/M 周期阻滞,通过Caspase途径诱导细胞凋亡,从而发挥抗肝癌活性。

这项研究得到了国家科技部、国家自然科学基金委、中国科学院和上海市科委的资助,研究成果将为肝癌的预防和治疗提供新思路。(生物谷Bioon.com)


参考文献:


Iron deprivation suppresses hepatocellular carcinoma growth in experimental studies

DOI:酒精诱发肝细胞凋亡的发病机制
AUTHORS:Qian Ba, Miao Hao, He Huang, Junmei Hou, Shichao Ge, Zhuzhen Zhang, Jun Yin, Ruiai Chu, Liang Hua Jiang, Fudi Wang, Kaixian Chen, Hong Liu, and Hui Wang
ABSTRACT:Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death and iron overload is a significant risk factor in the development of HCC. In this study we investigated the potential application of depriving iron by a novel iron chelator, thiosemicarbazone-24 (TSC24), in HCC treatment. Experimental Design:Two HCC cell lines and HFE knockout (HFE-/-) mice were used to determine iron chelation efficiency of TSC24. The anticancer effects of TSC24 on HCC were analyzed in vitro and in athymic xenograft mouse models. Results:Treatment with TSC24 significantly decreased the cellular iron concentration in hepatoma cells and the serum iron concentration in HFE-/- mice, by blocking iron uptake and interfering with normal regulation of iron levels. Moreover, the viability of HCC cell lines was reduced by TSC24. Confirming the mechanism of the agent, this decrease in viability could be partially rescued by addition of exogenous iron. TSC24 also suppressed tumor growth in athymic mice bearing human HCC xenografts in a concentration dependent manner without apparent toxicity in parallel with a decrease in the serum iron level. Further studies revealed that TSC24 efficiently triggered cell cycle arrest and apoptosis in Hep3B and HepG2 cell lines. Conclusions:TSC24 is a potent iron chelator that suppresses human HCC tumor growth by disrupting iron homeostasis, reducing available iron and triggering cell cycle arrest and apoptosis, without apparent host toxicity at effective doses. Thus, TSC24 shows great potential for the treatment of HCC.

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