Inhibition of cervical cancer cell proliferation and cervical tumorigenicity caused by farnesoid X receptor activation or over-expression is related to CDKN2A-p14ARF-MDM2-p53 pathway / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE Cervical cancer is the third most malignant tumor in the world. Farnesoid X receptor (FXR) is a member of nuclear receptor superfamily. It is highly expressed in liver, kidney and small intestine, while it showed low expression level in other tissues. It not only plays an important role in the metabolism of bile acids and sugars, but also in the production of chronic inflammation in the early stage of cancer, the proliferation and migration of tumor. Compared with the normal tissue, the expression of FXR in most tumor tissues decreased. But there is no correlation between cervical cancer and FXR. So we aimed to find out the relationship between FXR and cervical cancer. METHODS A clinical study using qPCR, western blot and immunohistochemistry detected the expression of FXR in tumor tissues and normal tissues of clinical patients. FXR was activated by agonists or over-expressed by lentivirus. MTT, clone formation and flow cytometry were used to detect the relationship between FXR and proliferation of cervical cell lines. Tumor growth ability of FXR was detected by nude mice tumorigenicity. The interaction between FXR and CDKN2A-p14ARF-MDM2-p53 pathway was detected by qPCR, Western blot and immunohistochemistry. RESULTS FXR was decreased in cancer tissues compared to normal control. Activation of FXR by agonist or constitutively- over- expression of FXR inhibited cervical cell proliferation. Over- expressed FXR attenuated Caski, Hela and Siha xenograft tumor growth in nude mice compared with control. Over-expression of FXR caused G1 cell-cycle arresting and up-regulated CDKN2A-p14ARF-MDM2-p53 pathway. CONCLUSION FXR inhibits cervical cancer cell proliferation and cervical tumorigenicity which is related to CDKN2A-p14ARF-MDM2-p53 pathway. Activation or overexpression of FXR may be a potential target for the treatment of cervical cancer.