Gambogic acid induces apoptosis in diffuse large B-cell lymphoma cells via inducing proteasome inhibition.
Gambogic acid induces apoptosis in diffuse large B-cell lymphoma cells via inducing proteasome inhibition.
复制标题
藤黄酸通过诱导蛋白酶体抑制诱导弥漫性大 B 细胞淋巴瘤细胞凋亡
DOI：
10.1038/srep09694
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发表时间：
2015-04-08
影响因子：
4.6
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Shi X;Lan X;Chen X;Zhao C;Li X;Liu S;Huang H;Liu N;Zang D;Liao Y;Zhang P;Wang X;Liu J
化疗耐药是提高弥漫性大B细胞淋巴瘤（DLBCL）患者生存率的一大挑战，尤其是活化B细胞样DLBCL（ABC-DLBCL）患者。因此，寻找新的药物治疗DLBCL是当务之急。藤黄酸（GA）是从中药藤黄中提取的一种小分子化合物，已被中国食品药品监督管理局批准用于癌症治疗的II期临床试验。在本研究中，我们研究了GA对DLBCL细胞（包括GCB-和ABC-DLBCL细胞）的细胞存活和凋亡的影响。我们发现GA在体外和体内均诱导GCB-和ABC-DLBCL细胞的生长抑制和凋亡，这与蛋白酶体功能障碍有关。这些发现为GA在DLBCL治疗中的潜在用途提供了重要的临床前证据，特别是在ABC-DLBCL治疗中。
Resistance to chemotherapy is a great challenge to improving the survival of patients with diffuse large B-cell lymphoma (DLBCL), especially those with activated B-cell-like DLBCL (ABC-DLBCL). Therefore it is urgent to search for novel agents for the treatment of DLBCL. Gambogic acid (GA), a small molecule derived from Chinese herb gamboges, has been approved for Phase II clinical trial for cancer therapy by Chinese FDA. In the present study, we investigated the effect of GA on cell survival and apoptosis in DLBCL cells including both GCB- and ABC-DLBCL cells. We found that GA induced growth inhibition and apoptosis of both GCB- and ABC-DLBCL cells in vitro and in vivo, which is associated with proteasome malfunction. These findings provide significant pre-clinical evidence for potential usage of GA in DLBCL therapy particularly in ABC-DLBCL treatment.