Thymoquinone inhibits growth and augments 5-fluorouracil-induced apoptosis in gastric cancer cells both in vitro and in vivo
Thymoquinone inhibits growth and augments 5-fluorouracil-induced apoptosis in gastric cancer cells both in vitro and in vivo
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DOI：
10.1016/j.bbrc.2011.12.063
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发表时间：
2012-01-13
影响因子：
3.1
通讯作者：
Dong, Weiguo
中科院分区：
文献类型：
--
作者：
Lei, Xiaofei;Lv, Xiaoguang;Dong, Weiguo
百里醌 (TQ) 是一种源自黑种草 (Nigella sativa) 生物活性成分的成分，已被证明对多种类型的人类癌症具有生物活性。然而，很少有研究探讨其对胃癌的影响。在此，我们提出第一份描述百里醌和 5-氟尿嘧啶 (5-FU) 对胃癌细胞体外和体内化学增敏作用的报告。研究表明，TQ预处理显着增加了体外5-FU诱导的胃癌细胞系的凋亡作用。此外，我们发现TQ通过介导抗凋亡蛋白bcl-2的下调、促凋亡蛋白bax的上调以及caspase-3和caspase-9的激活来增强5-FU诱导的胃癌细胞杀伤作用。除了体外结果外，在异种移植肿瘤小鼠模型中，TQ 与 5-FU 联合治疗比单独使用任一药物更有效。这些数据表明，TQ/5-FU联合治疗通过增强胃癌细胞中caspase-3和caspase-9的活化来诱导细胞凋亡。这些结果提供了体外和体内的分子证据，支持我们的结论，即百里醌可以激活 caspase-3 和 caspase-9，从而导致胃癌细胞对 5-FU 诱导的细胞死亡产生化学敏感性。 (C) 2011 Elsevier Inc. 保留所有权利。
Thymoquinone (TQ), a component derived from the bioactive constituent of black seed (Nigella sativa), has been shown to exert biological activity on various types of human cancers. However, there are few studies addressing its effects on gastric cancer. Here, we present the first report describing the chemosensitizirig effect of thymoquinone and 5-fluorouracil (5-FU) on gastric cancer cells both in vitro and in vivo. Studies have shown that pretreatment with TQ significantly increased the apoptotic effects induced by 5-FU in gastric cancer cell lines in vitro. Moreover, we found that TQ enhanced the 5-FU-induced killing of gastric cancer cells by mediating the downregulation of the anti-apoptotic protein bcl-2, the upregulation of the pro-apoptotic protein bax, and the activation of both caspase-3 and caspase-9. In addition to the in vitro results, it has been shown that the combined treatment of TQ with 5-FU represents a significantly more effective antitumor agent than either agent alone in a xenograft tumor mouse model. These data suggest that the TQ/5-FU combined treatment induces apoptosis by enhancing the activation of both caspase-3 and caspase-9 in gastric cancer cells. These results, which provide molecular evidence both in vitro and in vivo, support our conclusion that thymoquinone can activate caspase-3 and caspase-9 and thus result in the chemosensitisation of gastric cancer cells to 5-FU-induced cell death. (C) 2011 Elsevier Inc. All rights reserved.