Activated pregnane X receptor inhibits cervical cancer cell proliferation and tumorigenicity by inducing G2/M cell-cycle arrest

Yongdong Niu; Ziliang Wang; Haihua Huang; Shuping Zhong; Wenfeng Cai; Yangmin Xie; Ganggang Shi

doi:10.1016/j.canlet.2014.01.026

Activated pregnane X receptor inhibits cervical cancer cell proliferation and tumorigenicity by inducing G2/M cell-cycle arrest

Cancer Lett. 2014 May 28;347(1):88-97. doi: 10.1016/j.canlet.2014.01.026. Epub 2014 Jan 31.

Authors

Yongdong Niu¹, Ziliang Wang², Haihua Huang³, Shuping Zhong⁴, Wenfeng Cai¹, Yangmin Xie⁵, Ganggang Shi⁶

Affiliations

¹ Department of Pharmacology, Shantou University Medical College, Guangdong, China.
² Cancer Research Laboratory, Fudan University Shanghai Cancer Center, Department of Oncology, Fudan University, Shanghai, China.
³ Department of Pathology, Second Affiliated Hospital of Shantou University Medical College, Guangdong, China.
⁴ Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁵ Department of Experimental Animal Center, Medical College of Shantou University, Guangdong, China.
⁶ Department of Pharmacology, Shantou University Medical College, Guangdong, China. Electronic address: ggshi@stu.edu.cn.

PMID: 24486740
DOI: 10.1016/j.canlet.2014.01.026

Abstract

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.

Keywords: Cell cycle; Cervical cancer; Pregnane X receptor; Proliferation; Tumorigenicity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Division / physiology*
Cell Line, Tumor
Cell Proliferation*
Female
G2 Phase / physiology*
Heterografts
Humans
Mice
Mice, Inbred BALB C
Pregnane X Receptor
Real-Time Polymerase Chain Reaction
Receptors, Steroid / physiology*
Reverse Transcriptase Polymerase Chain Reaction
Uterine Cervical Neoplasms / pathology*

Substances

Pregnane X Receptor
Receptors, Steroid