DOK1/PPARgamma pathway mediates anti-tumor ability of all-trans retinoic acid in breast cancer MCF-7 cells
DOK1/PPARgamma pathway mediates anti-tumor ability of all-trans retinoic acid in breast cancer MCF-7 cells
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DOI：
10.1016/j.bbrc.2017.04.018
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发表时间：
2017-05-27
影响因子：
3.1
通讯作者：
Yao, Feng
中科院分区：
文献类型：
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作者：
Ding, Xiaojun;Wang, Wenjie;Yao, Feng
以往的研究表明，全反式维甲酸（ATRA）在许多肿瘤，包括乳腺癌的抗癌作用，但其潜在的分子机制仍然知之甚少。本研究发现ATRA处理后MCF-7细胞增殖受到抑制，凋亡增加，同时沿着DOK 1表达增强。DOK 1基因敲低可阻断ATRA对细胞增殖和凋亡的影响。此外，DOK 1的基因沉默可以抑制PPAR γ的表达及其活性。此外，其特异性抑制剂GW 9662对PPAR γ的失活逆转了ATRA对细胞增殖和凋亡的影响。总之，这些结果表明，ATRA增强的DOK 1表达激活了PPAR γ，导致MCF-7细胞中细胞增殖的抑制和细胞凋亡的增强。(C)2017爱思唯尔公司All rights reserved.
Previous studies have showed the anticancer effect of the all-trans retinoic acid (ATRA) in many tumors including breast cancer; however, the underlying molecular mechanism is still poorly understood. This study experimentally revealed that ATRA treatment inhibited MCF-7 cell proliferation and promoted its apoptosis, along with an enhanced expression of docking protein 1 (DOK1). ATRA's effects on cell proliferation and apoptosis were prevented by DOK1 knockdown. In addition, the genetic silence of DOK1 can inhibit PPAR gamma expression and its activity. Moreover, inactivation of PPAR gamma by its specific inhibitor GW9662 reversed the impacts of ATRA on cell proliferation and apoptosis. Taken together, these results indicate that ATRA-enhanced expression of DOK1 activates PPAR gamma leading to inhibition of cell proliferation and enhancement of cell apoptosis in MCF-7 cell. (C) 2017 Elsevier Inc. All rights reserved.