核受体PXR对人结肠癌细胞增殖和化疗敏感性的影响

Roles of Pregnane X Receptor for Proliferation and Drug Resistance in Human Colon Cancer Cells

目的:探讨核受体PXR在结肠癌细胞增殖和化疗敏感性中的作用。方法:分别用RT-PCR和westernblot方法检测PXR在人结肠癌细胞株LS174T、LOVO、HT29、HCT116中的表达情况。通过质粒稳定转染方法建立PXR敲低的细胞株。用MTT方法分析利福平活化PXR或稳定转染敲低PXR后,细胞增殖和化疗敏感性的改变。结果:在结肠癌细胞株LS174T、LOVO、HT29、HCT116中,LS174T细胞的PXR表达水平最高。利福平处理后,LS174T细胞中PXR表达增强。利福平活化PXR或稳定转染敲低PXR后,相应地促进或抑制细胞增殖,降低或提高细胞对化疗药物的敏感性。结论:PXR能促进结肠癌细胞增殖,提高细胞对化疗药物的敏感性,可能在结肠癌多药耐药机制中具有重要作用。

Objective： To study the roles of PXR in human colon cancer cell proliferation and drug resistance. Methods： The mRNA and protein levels of PXR in colon cancer cells were determinded by RT-PCR and western blot. LS174T cells were transfected with PXR shRNA products, and selected by G418. Cell activity with or without the chemotherapeutic agents was assayed by MTT after PXR was activated by rifampicin or knocked down by PXR shRNAs. Results： The both mRNA and protein level of PXR in LS174T cells was the highest among LS174T, HCT116, LOVO and HT29 cells. The expression of PXR was increased after rifampicin treatment. PXR being activated or knocked down, accordingly increased or inhibited the cell proliferation, and enhanced or reduced cells resistance to the chemotherapeutic agents. Conclusion： PXR could affect the colon cancer cell proliferation and sensitivity to the chemotherapeutic agents and it may play an important role in colon cancer drug resistance.