从中医药宝库中发掘治疗淋巴瘤的新药是非常重要而宝贵的途径。我们发现华蟾素单药治疗中晚期淋巴瘤具有肯定的疗效，初步实验证实，华蟾素抗肿瘤主要成分蟾毒灵可诱导淋巴瘤细胞株凋亡，mRNAseq分析及western提示其抑制mutp53蛋白，RT-PCR提示p63/p73上调及survivin下调，我们推测蟾毒灵靶向抑制mutp53激活p63/p73促进肿瘤凋亡。本研究拟通过在Raji细胞中过表达及下调mutp53，其后体内外予蟾毒灵干预明确其作用的分子机制。利用微生物细胞悬浮体系筛选出高效低毒的蟾毒灵衍生物CNJ-2，通过体内外实验研究，明确CNJ-2具有与蟾毒灵相同的分子机制。通过患者来源的淋巴瘤活检组织异种移植NCG小鼠建立PDTX模型，进一步验证CNJ-2治疗淋巴瘤的体内疗效及与mutp53的关系, 从而阐明CNJ-2治疗淋巴瘤的分子靶点和作用机制，为开发淋巴瘤的新型靶向药物打下基础。

Discovering new drug from traditional Chinese medicine is a very important and valuable road. We found that Cinobufacin has certain curative effects for the treatment of advanced lymphomain in our previous clinical studies. Bufalin is the main antitumor component of cinobufotalin. We found bufalin can induce apoptosis of Raji lymphoma cells and significantly inhibit the mutant p53 (mutp53) expression, increase p63/p73 expression. We hypothesized that bufalin targeted inhibition mutp53 and activate p63 / p73 promotes tumor apoptosis. We design overexpression and shRNA mutp53 in Raji cells, followed by Bufalin treatment in vitro and in vivo to clarify its molecular mechanism. CNJ-2, the novel bufalin derivative with high efficiency and low toxicity were screened by microbial cell suspensions system. We next to reveal CNJ-2 has a same molecular mechanism with bufalin through the in vitro and in vivo experiment. By patient-derived xenograft lymphoma biopsy transplant NCG mouse establish PDTX model to further validate the efficacy of CNJ-2 treatment of lymphoma in vivo and its relationship with mutp53. Thereby clarify the molecular targets and mechanisms of CNJ-2 for treatment of lymphoma. This work may helpful for development of new targeting drugs to treatment of lymphoma.