Synergistic anticancer effects of triptolide and celastrol, two main compounds from thunder god vine.
Synergistic anticancer effects of triptolide and celastrol, two main compounds from thunder god vine.
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雷公藤中的两种主要化合物雷公藤甲素和雷公藤红素的协同抗癌作用
DOI：
10.18632/oncotarget.5411
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发表时间：
2015-10-20
期刊：
影响因子：
--
通讯作者：
Shi Z
中科院分区：
文献类型：
--
作者：
Jiang QW;Cheng KJ;Mei XL;Qiu JG;Zhang WJ;Xue YQ;Qin WM;Yang Y;Zheng DW;Chen Y;Wei MN;Zhang X;Lv M;Chen MW;Wei X;Shi Z
雷公藤甲素和雷公藤红素是从雷公藤中分离得到的两种主要活性化合物，具有较强的抗癌活性。然而，雷公藤甲素与雷公藤红素联合使用的抗癌效果尚不清楚。在本研究中，我们证明雷公藤甲素与雷公藤红素联合使用可协同诱导癌细胞生长抑制、细胞周期阻滞于G2/M期和凋亡，并增加细胞内ROS积累。用活性氧清除剂n -乙酰- l-半胱氨酸预处理可显著阻断雷公藤甲素和雷公藤红素共处理诱导的细胞凋亡。单用雷公藤红素治疗可导致HSP90客户蛋白（包括survivin、AKT、EGFR）的表达降低，而加入雷公藤红素可增强这种表达。雷公藤甲素可抑制雷公藤酚诱导的HSP70和HSP27的表达。在移植瘤裸鼠中，雷公藤甲素与雷公藤红素低剂量联用可显著抑制肿瘤生长，无明显毒性。总的来说，雷公藤甲素与雷公藤红素联合在体内和体外都显示出出色的协同抗癌作用，这表明这种有益的组合可能为癌症患者提供一个有希望的治疗选择。
Triptolide and celastrol are two main active compounds isolated from Thunder God Vine with the potent anticancer activity. However, the anticancer effect of triptolide in combination with celastrol is still unknown. In the present study, we demonstrated that the combination of triptolide with celastrol synergistically induced cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the increased intracellular ROS accumulation in cancer cells. Pretreatment with ROS scavenger N-acetyl-L-cysteine dramatically blocked the apoptosis induced by co-treatment with triptolide and celastrol. Treatment with celastrol alone led to the decreased expressions of HSP90 client proteins including survivin, AKT, EGFR, which was enhanced by the addition of triptolide. Additionally, the celastrol-induced expression of HSP70 and HSP27 was abrogated by triptolide. In the nude mice with xenograft tumors, the lower-dose combination of triptolide with celastrol significantly inhibited the growth of tumors without obvious toxicity. Overall, triptolide in combination with celastrol showed outstanding synergistic anticancer effect in vitro and in vivo, suggesting that this beneficial combination may offer a promising treatment option for cancer patients.