豹蛙酶的抗肿瘤作用研究进展

豹蛙酶(onconase)又称抗瘤酶、P30 蛋白等,属核糖核酸酶 A超家族成员.豹蛙酶是目前唯一用于临床试验阶段的核糖核酸酶,它的核糖核酸酶活性低,细胞毒性较强,对体内外多种肿瘤有很强的杀伤作用,是当前全球重点研究的 100 种新药之一.豹蛙酶在北极蛙的早期胚胎中被首次发现,它主要通过破坏RNA从而抑制蛋白质合成,诱导肿瘤细胞凋亡,此外还有其他抗肿瘤机制,如影响特定基因的表达和破坏端粒酶RNA.豹蛙酶和其他抗癌药物联合应用会增强抗癌药物的抗肿瘤细胞毒性.目前,豹蛙酶对小细胞肺癌和其他实体肿瘤的治疗处于Ⅰ期或Ⅱ期临床试验,对恶性间皮瘤的治疗处于Ⅲ期临床试验阶段,是潜在的治疗恶性间皮瘤的药物.

Review of the anti-tumor role of onconase

Onconase, also called P30 protein, is a member of RNase A superfamily, and is the only enzyme of this class that reached clinical trials. It has weak RNase activity and strong cytotoxicity to various tumor cells in vitro as well as EM>in vivo/EM>, and it is one of the 100 new drugs in research recently. Onconase was first found in early embryos of leopard frog (Rana pipiens), and onconase can trigger apoptosis of tumor cells via degrading RNA, leading to inhibiting sythesis of protein. In addition, onconase has other anticancer mechanisms, such as influencing expression of specific genes and destroying telomerase RNA. Onconase could also enhance the cytotoxicity of other anticancer drugs. The phase I and phase I/II clinical trials of onconase as a single therapeutic agent in patients with non-small cell lung cancer and other solid tumors is conducting, and the phase III human clinical trials for the treatment of unresectable malignant mesothelioma (MM) is undergoing. Onconase may serve as a second-line therapy for MM.