Activated pregnane X receptor inhibits cervical cancer cell proliferation and tumorigenicity by inducing G2/M cell-cycle arrest.
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.
Department of Pharmacology, Shantou University Medical College, Guangdong, China.
Yongdong
Y
Niu
Cancer Research Laboratory, Fudan University Shanghai Cancer Center, Department of Oncology, Fudan University, Shanghai, China.
Ziliang
Z
Wang
Department of Pathology, Second Affiliated Hospital of Shantou University Medical College, Guangdong, China.
Haihua
H
Huang
Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Shuping
S
Zhong
Department of Pharmacology, Shantou University Medical College, Guangdong, China.
Wenfeng
W
Cai
Department of Experimental Animal Center, Medical College of Shantou University, Guangdong, China.
Yangmin
Y
Xie
Department of Pharmacology, Shantou University Medical College, Guangdong, China. Electronic address: ggshi@stu.edu.cn.
Ganggang
G
Shi
D000818:Animals; D002455:Cell Division / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D016195:G2 Phase / Q000502:physiology*; D064593:Heterografts; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D000077297:Pregnane X Receptor; D060888:Real-Time Polymerase Chain Reaction; D011987:Receptors, Steroid / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000473:pathology*
D000077297:Pregnane X Receptor; D011987:Receptors, Steroid
Cell cycle; Cervical cancer; Pregnane X receptor; Proliferation; Tumorigenicity