结肠癌细胞核受体PXR表达对CPT-11化疗效果的影响

Effect of pregnane X receptor (PXR) expression on chemotherapeutic sensitivity to CPT-11 in colon cancer cells

目的:探讨结肠癌细胞核受体PXR表达的变化对CPT-11化疗效果的影响。方法:用Western blot方法检测PXR蛋白在人结肠癌细胞株LS174T、HT29和HCT116中的表达。通过莱菔硫烷、利福平分别敲低或上调PXR受体的表达,利用MMT或流式细胞术研究其表达下调或上调对细胞增殖和凋亡的影响。结果:3株结肠癌细胞株LS174T、HT29、HCT116中,LS174T细胞的PXR表达水平最高(P=0.000)。莱菔硫烷处理后,LS174T细胞中PXR表达明显减弱(P=0.000),CPT-11作用后,细胞增殖明显受到抑制(P=0.013),对CPT-11敏感性增强;同时利用利福平处理后,LS174T细胞中PXR表达增强(P=0.000),CPT-11作用后,细胞增殖明显加速(P=0.019),对CPT-11敏感性降低。结论:结肠癌细胞核受体PXR表达的变化对于CPT-11化疗敏感性具有十分重要的影响,其可能在结肠癌耐药机制中具有重要作用。

Objective ：To investigate the effects of PXR expression changes in human colon cancer cell on chemotherapeutic sensitivity to CPT-11. Methods：The expression levels of PXR in human colon cancer ceils LS174T,HT29 and HCT116 were measured by Western blot. After upregulation or downregulation of PXR expression by rifampicin or sulforaphane, cell growth was studied by MTT assay and cell cycle was measured by flow cytometry. Results ：The expression levels of PXR in LS174T cell were the highest among human colon cancer cells LS174T,HT29 and HCT116 （P=0.000）. After being treated with sulforaphane, PXR expression in LS174T cell was significantly down-regulated （P=0.000）and cell proliferation was suppressed after being treated with CPT-11 （P=0.013）, so the chemotherapeutic sensitivity of LS 174T cell to CPT-11 was significantly increased. By contrast, after being treated with rifampicin, PXR expression in LS174T cell was significantly up-regulated（P=0.000） and cell proliferation was enhanced（P=0.019）,so the chemotherapeutic sensitivity to CPT-11 was significantly decreased. Conclusion：The expression changes of PXR in human colon cancer cell have significant effect on chemotherapeutic sensitivity to CPT-11 ,and this mechanism may play an important role in the drug resistance mechanisms of human colon cancer.