The study of iron chelators as cancer chemotherapeutic agents is still in its infancy. Accordingly, there is a need to optimize new chelating molecules for iron chelation therapy and cancer treatment. Previous studies have demonstrated that the ligand tris(1-pyrazolyl) borohydride and its derivates were able to chelate ferrous iron, but very little research focused on their biological properties and applications in cancer treatment. So, in this study, several boron-pyrazole derivatives were chosen for the examination of their effects on the proliferation of human hepatocellular carcinoma (HCC) cell lines. The results suggested that potassium tris(4-methyl-1-pyrazolyl) borohydride (KTp^4-Me) exhibited the most potent anti-tumor activities among the candidates. Hence, the antiproliferative activity and the iron chelating capacity of the iron chelator KTp^4-Me in HCC cell lines HepG2 and Hep3B were characterized. KTp^4-Me could disrupt cell iron uptake and affect signaling pathways of iron regulation in HCC cell lines and induced the expression of TfR1 and HIF-1α in a concentration-dependent manner, which was a typical cell response to iron deficiency. Moreover, KTp^4-Me arrested cell cycle in S phase and induced cell apoptosis in both Hep3B and HepG2 cells. Overall, our results provide a promising starting point and the possibility of the future development and applications of KTp^4-Me in HCC therapy.

铁螯合剂作为癌症化学治疗剂的研究仍处于起步阶段。因此，需要优化用于铁螯合治疗和癌症治疗的新的螯合分子。先前的研究表明，配体三（1-吡唑基）硼氢化物及其衍生物能够螯合亚铁，但很少有研究关注它们的生物学特性和在癌症治疗中的应用。因此，在这项研究中，选择了几种硼-吡唑衍生物以检查它们对人肝细胞癌（HCC）细胞系增殖的影响。结果表明三（4-甲基-1-吡唑基）硼氢化钾（KTp ^4-Me）在候选人中表现出最有效的抗肿瘤活性。因此，表征了HCC细胞系HepG2和Hep3B中铁螯合剂KTp ^4-Me的抗增殖活性和铁螯合能力。KTp ^4-Me可能破坏细胞对铁的吸收并影响HCC细胞系中铁调节的信号通路，并以浓度依赖的方式诱导TfR1和HIF-1α的表达，这是典型的细胞对铁缺乏的反应。此外，KTp ^4-Me阻滞了S期的细胞周期，并诱导了Hep3B和HepG2细胞的细胞凋亡。总体而言，我们的结果提供了一个有希望的起点，以及未来开发和应用KTp ^4-Me在HCC治疗中的可能性。