Perifosine sensitizes curcumin-induced anti-colorectal cancer effects by targeting multiple signaling pathways both in vivo and in vitro
Perifosine sensitizes curcumin-induced anti-colorectal cancer effects by targeting multiple signaling pathways both in vivo and in vitro
复制标题
Perifosine 通过靶向体内和体外多种信号通路来增强姜黄素诱导的抗结直肠癌作用
DOI：
10.1002/ijc.27548
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发表时间：
2012-12-01
影响因子：
6.4
通讯作者：
Lu, Pei-Hua
中科院分区：
文献类型：
--
作者：
Chen, Min-Bin;Wu, Xiao-Yang;Lu, Pei-Hua
我们的研究表明，姜黄素和口服生物活性烷基磷脂周磷脂联合应用，在体外和体内都能显著增加结直肠癌细胞的凋亡率，并显著抑制细胞的生长。这种新的联合方案导致多种细胞信号通路的改变，包括Akt和核因子-β的失活，以及c-jun氨基末端激酶的激活和内质网应激。此外，Perifosine和姜黄素协同增加细胞内活性氧和神经酰胺的水平，下调细胞周期蛋白D1和Bcl-2的表达。这些在分子水平上的变化共同解释了癌细胞的凋亡和生长抑制。我们得出结论，Perifosine通过调节多个信号通路使结直肠癌细胞对姜黄素增敏。加用Perifosine和姜黄素可能是治疗结直肠癌和其他侵袭性肿瘤的一种有效的治疗方案。
Our study shows that coadministration of curcumin and an orally bioactive alkylphospholipid perifosine results in a significant increase in colorectal cancer cell apoptosis and a marked inhibition of cell growth both in vitro and in vivo. This novel combinatorial regimen leads to changes of multiple cell signaling pathways including inactivation of Akt and nuclear factor-?B as well as activation of c-Jun N-terminal kinases and endoplasmic reticulum stress. Further, perifosine and curcumin synergistically increase intracellular level of reactive oxygen species and ceramide, and downregulate the expression of cyclin D1 and Bcl-2 in colorectal cancer cells. These changes at molecular level together account for the cancer cell apoptosis and growth inhibition. We conclude that perifosine sensitizes colorectal cancer cells to curcumin by modulating multiple signaling pathways. Adding perifosine with curcumin may represent an effective therapy regimen against colorectal cancers, and possible other aggressive tumors.