Allicin sensitizes hepatocellular cancer cells to anti-tumor activity of 5-fluorouracil through ROS-mediated mitochondrial pathway.
Allicin sensitizes hepatocellular cancer cells to anti-tumor activity of 5-fluorouracil through ROS-mediated mitochondrial pathway.
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大蒜素通过 ROS 介导的线粒体途径使肝细胞癌细胞对 5-氟尿嘧啶的抗肿瘤活性敏感。
DOI：
10.1016/j.jphs.2016.04.017
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发表时间：
2016-08
期刊：
影响因子：
--
通讯作者：
Liu Li
中科院分区：
文献类型：
--
作者：
Zou Xuejing;Liang Jiyun;Sun Jingyuan;Hu Xiaoyun;Lei Ling;Wu Dehua;Liu Li
耐药和肝功能障碍是限制肝细胞癌化疗应用的两大因素。已有研究表明，大蒜素具有保肝、抗肿瘤作用。因此，大蒜素可能是一种理想的肝癌化疗方案的增强剂。在体内实验中，大蒜素(5 mg/kg/d，隔日1次，连续3周)和5-FU(20 mg/kg/d，连续5天)联合治疗组对人肝癌裸鼠移植瘤的生长有明显的抑制作用。联合治疗组与5-FU单独治疗组相比，细胞凋亡率较高。与二甲基亚砜、大蒜素和5-FU单独作用相比，大蒜素和5-FU联合作用可提高细胞内活性氧(ROS)水平，降低线粒体膜电位(ΔΨm)，激活caspase3和PARP，下调Bcl2表达。此外，ROS抑制剂抗氧化剂N-乙酰半胱氨酸(NAC)可阻断激活的caspase-3和PARP的增加。综上所述，这是首次证实大蒜素通过ROS介导的线粒体途径敏化5-FU诱导肝癌细胞凋亡。这些结果为大蒜素联合5-FU作为一种新的肝癌化疗方案提供了证据。
Drug resistance and hepatic dysfunction are the two major factors that limit the application of chemotherapy for hepatocellular carcinoma (HCC). It has been reported that allicin has the hepatic protective effect and antitumor activity. Hence allicin may be an ideal enhancer to chemotherapy regimen of HCC. In the present study, we demonstrated that allicin enhanced 5-fluorouracil (5-FU) inducing cytotoxicity in HCC cells.In vivoexperiment, combined treatment group with allicin (5 mg/kg/d; every two days for 3 weeks) and 5-FU (20 mg/kg/d; 5 consecutive days) showed a dramatic inhibitory effect on the growth of HCC xenograft tumors in nude mice. The co-treatment group showed highly apoptotic level compared with 5-FU treated alone. Cells combined treatment with allicin and 5-FU increased intracellular reactive oxygen species (ROS) level, reduced mitochondrial membrane potential (ΔΨm), activated caspase-3 and PARP, and down-regulated Bcl-2 compared with DMSO, allicin and 5-FU treated alone. Moreover, the increase of activated caspase-3 and PARP was blocked by the ROS inhibitor antioxidant N-acetyl cysteine (NAC). In conclusion, this is the first study to demonstrate that allicin sensitized HCC cells to 5-FU induced apoptosis through ROS-mediated mitochondrial pathway. These results provided evidences for the combination used of allicin and 5-FU as a novel chemotherapy regimen in HCC.
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