Activated pregnane X receptor inhibits cervical cancer cell proliferation and tumorigenicity by inducing G2/M cell-cycle arrest |
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| Authors: | Yongdong Niu Ziliang Wang Haihua Huang Shuping Zhong Wenfeng Cai Yangmin Xie Ganggang Shi |
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| Affiliation: | 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 |
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| 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. |
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| Keywords: | CCK-8 assay, Cell Counting Kit-8 assay CYP3A4, cytochrome p450 3A4 CUL, Cullin DMEM, Dulbecco&rsquo s modified Eagle&rsquo s medium DMSO, dimethyl sulfoxide h, human HPV, human papilloma virus IHC, immunohistochemistry MDR1, multidrug resistance 1 PCN, Pregnenolone 16α carbonitrile PCNA, proliferating cell nuclear antigen PI, propidium iodide PXR, pregnane X receptor qRT-PCR, quantitative real-time polymerase chain reaction RIF, rifampicin RT-PCR, reverse-transcriptase polymerase chain reaction |
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