The incidence of HCC continues to increase rapidly in recent years. the principle of developing anti-HCC drugs is to specifically kill tumor cells, without affecting the function of normal cells. Here we synthesized a novel protonic compound bis(5-amino-1,10-phenanthroline) (P-BAP), and the antitumor activity was explored in vitro and in vivo. The results showed that P-BAP could selectively inhibit the proliferation of tumor cells, and induce HCC apoptosis. In HCC-bearing mice, P-BAP could effectively retard the tumor growth, even completely eliminate the tumors at the dose of 5 mg/kg, and meanwhile P-BAP had no significant effect on mouse body weight. Mechanism analysis revealed that P-BAP could down-regulate the protein expressions of pleomorphic adenoma gene like-2 (PLAGL2), HIF-1α and β-catenin, and up-regulate the levels of pro-apoptotic protein BAX and BNIP3. In addition, P-BAP could reduce mitochondrial respiratory chain complex activities, leading to insufficient ATP production. The study provides a new approach for designing selective antitumor drugs, and suggests that P-BAP would be a potential candidate for HCC therapy.

近年来，HCC的发病率持续快速上升。开发抗HCC药物的原则是特异性杀伤肿瘤细胞，而不影响正常细胞的功能。在这里，我们合成了一种新型质子化合物双（5-氨基-1,10-菲咯啉）（P-BAP），并在体外和体内探索了抗肿瘤活性. 结果表明，P-BAP可以选择性地抑制肿瘤细胞的增殖，诱导肝癌细胞凋亡。在荷HCC小鼠中，P-BAP在5 mg/kg剂量下可有效延缓肿瘤生长，甚至完全消除肿瘤，同时P-BAP对小鼠体重无显着影响。机制分析表明，P-BAP可以下调多形性腺瘤基因like-2（PLAGL2）、HIF-1α和β-catenin的蛋白表达，上调促凋亡蛋白BAX和BNIP3的水平。此外，P-BAP 可以降低线粒体呼吸链复合物的活性，导致 ATP 产生不足。该研究为设计选择性抗肿瘤药物提供了一种新方法，并表明 P-BAP 将成为 HCC 治疗的潜在候选者。