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Aplysin Sensitizes Cancer Cells to TRAIL by Suppressing P38 MAPK/Survivin Pathway

文献类型： 外文期刊

作者： Liu, Jia 1 ; Ma, Leina 3 ; Wu, Ning 1 ; Liu, Ge 1 ; Zheng, Lanhong 4 ; Lin, Xiukun 1 ;

作者机构： 1.Chinese Acad Sci, Inst Oceanol, Qingdao 266071, Peoples R China

2.Univ Chinese Acad Sci, Grad Sch, Beijing 100049, Peoples R China

3.Ocean Univ China, Sch Med & Pharm, Dept Mol Biol, Qingdao 266003, Peoples R China

4.Chinese Acad Fishery Sci, Yellow Sea Fisheries Res Inst, Qingdao 266071, Peoples R China

5.Capital Med Univ, Dept Pharmacol, Beijing 100069, Peoples R China

关键词： aplysin;TRAIL;p38 MAPK;survivin

期刊名称：MARINE DRUGS （ 影响因子：5.118； 五年影响因子：5.951 ）

ISSN： 1660-3397

年卷期： 2014 年 12 卷 9 期

页码：

收录情况： SCI

摘要： TNF-related apoptosis-inducing ligand (TRAIL) is a tumor-selective apoptosis inducer and has been shown to be promising for treating various types of cancers. However, the application of TRAIL is greatly impeded by the resistance of cancer cells to its action. Studies show that overexpression of some critical pro-survival proteins, such as survivin, is responsible for TRAIL resistance. In this study, we found that Aplysin, a brominated compound from marine organisms, was able to restore the sensitivity of cancer cells to TRAIL both in vitro and in vivo. Aplysin was found to enhance the tumor-suppressing capacity of TRAIL on several TRAIL-resistant cancer cell lines. TRAIL-induced apoptosis was also potentiated in A549 and MCF7 cells treated with Aplysin. Survivin downregulation was identified as a mechanism by which Aplysin-mediated TRAIL sensitization of cancer cells. Furthermore, the activation of p38 MAPK was revealed in Aplysin-treated cancer cells, and its inhibitor SB203580 was able to abrogate the promoting effect of Aplysin on the response of cancer cells to TRAIL action, as evidenced by restored survivin expression, elevated cell survival and reduced apoptotic rates. In conclusion, we provided evidence that Aplysin acts as a sensitizer for TRAIL and its effect on p38 MAPK/survivin pathway may partially account for this activity. Considering its low cytotoxicity to normal cells, Aplysin may be a promising agent for cancer treatment in combination with TRAIL.

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[1]p38 MAPK Signaling Mediates Mitochondrial Apoptosis in Cancer Cells Induced by Oleanolic Acid. Liu, Jia,Wu, Ning,Liu, Ge,Lin, Xiu-Kun,Zheng, Lan-Hong,Ma, Lei-Na,Liu, Ge,Lin, Xiu-Kun,Zhong, Jia-Teng. 2014

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