Cinobufotalin is a main cardiac toxin in toad, it is a novel anti-HCC agent, it induces growth inhibition and apoptosis in cultured HCC cells through ceramide production. Cinobufotalin is also an effective reversal agent for the multidrug resistance of tumors, it can reverse the adriamycin-resistance in Raji/ADR cells and the expression of P-gp and MRP-1 proteins. Cinobufotalin can promote the dendritic cells(DCs) derived from peripheral blood of patients with chronic hepatitis B to mature and effectively enhance its(the DCs') capabilities, therefore the treatment of cinobufotalin may potentiate the antiviral immunity of the patients with chronic hepatitis B(CHB).

肝细胞癌（HCC）是一种高度侵袭性和致命性的肿瘤。本研究旨在探究来自蟾蜍毒中提取的一种Bufadienolide类化合物Cinobufotalin对培养的HCC细胞的抗癌活性及其作用机制。方法与结果：我们发现Cinobufotalin（以nmol/L计）显著抑制HCC细胞的生长和存活，同时诱导细胞发生大量凋亡。此外，Cinobufotalin抑制了鞘氨醇激酶1（SphK1）的活性，并诱导了促凋亡的神经酰胺产生。脂酰胺合成酶-1小干扰RNA（shRNA）-耗竭抑制了Cinobufotalin诱导的神经酰胺产生和HCC细胞凋亡。另一方面，葡萄糖鞘脂酰胺合成酶（GCS）抑制剂1-苯基-2-癸酰胺基-3-吗啉基-1-丙醇（PDMP）促进了Cinobufotalin诱导的神经酰胺产生和细胞凋亡。与Cinobufotalin类似，SphK1抑制剂II（SKI-II）增加了细胞内神经酰胺水平并促进HCC细胞凋亡。最后，我们观察到Cinobufotalin在HepG2细胞中使Akt-S6K1信号通路失活，这一过程再次被脂酰胺合成酶-1 shRNA-耗竭所抑制。结论：总之，本研究结果表明Cinobufotalin通过促进神经酰胺产生来抑制HCC细胞的生长并诱导凋亡。Cinobufotalin可能作为一种新型抗HCC化合物进行研究。