Activated pregnane X receptor inhibits cervical cancer cell proliferation and tumorigenicity by inducing G2/M cell-cycle arrest
Activated pregnane X receptor inhibits cervical cancer cell proliferation and tumorigenicity by inducing G2/M cell-cycle arrest
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DOI：
10.1016/j.canlet.2014.01.026
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发表时间：
2014-05-28
期刊：
影响因子：
9.7
通讯作者：
Shi, Ganggang
中科院分区：
文献类型：
--
作者：
Niu, Yongdong;Wang, Ziliang;Shi, Ganggang
孕烷X受体（PXR）调节女性生殖组织细胞增殖和癌变。我们发现PXR在宫颈细胞和组织样品中表达。与正常对照相比，癌组织中的PXR较低或大大减少。在功能上，利福平激活人PXR或异位表达组成性激活的人VP-PXR抑制宫颈细胞增殖。与对照组相比，组成型激活的VP-PXR减弱了裸鼠中CaSki和HeLa异种移植肿瘤的生长。PXR通过引起G2/M期细胞阻滞而抑制细胞增殖，涉及Cullin 1 -3、MAD 2L 1的上调以及ANAPC 2和CDKN 1A的下调。我们的数据表明，PXR信号抑制肿瘤细胞增殖在体外和宫颈癌生长在体内。(C)2014爱思唯尔爱尔兰有限公司版权所有。
Pregnane X receptor (PXR) regulates cell proliferation and carcinogenesis in female reproductive tissue. We showed that PXR was expressed in cervical cells and tissue samples. PXR were lower or greatly diminished in cancer tissues compared to normal control. Functionally, activation of human PXR by rifampicin or ectopic expression of constitutively-activated human VP-PXR inhibited cervical cell proliferation. Constitutively-activated VP-PXR attenuated CaSki and HeLa xenograft tumor growth in nude mice compared with control. The cellular proliferation inhibition of PXR by causing G2/M cell-cycle arrest is involved up-regulation of Cullin1-3, MAD2L1, and down-regulation of ANAPC2 and CDKN1A. Our data suggests that PXR signaling inhibits tumor cell proliferation in vitro and cervical carcinoma growth in vivo. (C) 2014 Elsevier Ireland Ltd. All rights reserved.