Pregnane X receptor suppresses proliferation and tumourigenicity of colon cancer cells

Abstract

Pregnane X receptor (PXR) is a nuclear receptor that regulates the metabolism and disposition of various xenobiotics and endobioitics. We investigated a novel PXR function in regulating colon tumourigenesis in this study. Histochemistry, transfection, cell proliferation assay, anchorage-α-dependent assay, xenograft, immunohistochemistry, immunofluorescence flow cytometry. Using histochemistry analysis, we found that PXR expressions were lost or greatly diminished in many colon tumours. Ectopic expression of human PXR through stable transfection of PXR into colon cancer cell line HT29 significantly inhibited cell proliferation as determined by cell proliferation assay and anchorage-independent assay. Pregnane X receptor suppressed significantly HT29 xenograft tumour growth in nude mice compared with control (310±6.2 vs 120±6 mg, P0/G₁ cell-cycle arrest. p21^WAF1/CIP1 expression was markedly elevated whereas E2F1 expression was inhibited by PXR. PXR inhibits the proliferation and tumourigenicity of colon cancer cells by controlling cell cycle at G₀/G₁ cell phase by regulating p21^WAF1/CIP1 and E2F/Rb pathways.