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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.