Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Exp Cell Res. 2012 Apr 15;318(7):819-27. doi: 10.1016/j.yexcr.2012.02.004. Epub 2012 Feb 14.
Chemoprevention would be a desirable strategy to avoid duodenectomy in patients with familial adenomatous polyposis (FAP) suffering from duodenal adenomatosis. We investigated the in vitro effects on cell proliferation, apoptosis, and COX-2 expression of the potential chemopreventives celecoxib and tauro-ursodeoxycholic acid (UDCA). HT-29 colon cancer cells and LT97 colorectal micro-adenoma cells derived from a patient with FAP, were exposed to low dose celecoxib and UDCA alone or in combination with tauro-cholic acid (CA) and tauro-chenodeoxycholic acid (CDCA), mimicking bile of FAP patients treated with UDCA. In HT-29 cells, co-treatment with low dose celecoxib and UDCA resulted in a decreased cell growth (14-17%, p<0.01). A more pronounced decrease (23-27%, p<0.01) was observed in LT97 cells. Cell growth of HT-29 cells exposed to 'artificial bile' enriched with UDCA, was decreased (p<0.001), either in the absence or presence of celecoxib. In LT97 cells incubated with 'artificial bile' enriched with UDCA, cell growth was decreased only in the presence of celecoxib (p<0.05). No clear evidence was found for involvement of proliferating cell nuclear antigen, caspase-3, or COX-2 in the cellular processes leading to the observed changes in cell growth. In conclusion, co-treatment with low dose celecoxib and UDCA has growth inhibitory effects on colorectal adenoma cells derived from a patient with FAP, and further research on this combination as promising chemopreventive strategy is desired.
化学预防将是避免家族性腺瘤性息肉病（FAP）患者因十二指肠腺瘤病而行十二指肠切除术的理想策略。我们研究了潜在的化学预防药物塞来昔布和牛磺熊去氧胆酸（UDCA）对细胞增殖、凋亡和 COX-2 表达的体外影响。HT-29 结肠癌细胞和 LT97 结直肠微腺瘤细胞源自 FAP 患者，单独或联合牛磺胆酸（CA）和牛磺鹅去氧胆酸（CDCA）暴露于低剂量塞来昔布和 UDCA 中，模拟 FAP 患者用 UDCA 治疗的胆汁。在 HT-29 细胞中，低剂量塞来昔布和 UDCA 的联合治疗导致细胞生长减少（14-17%，p<0.01）。在 LT97 细胞中观察到更明显的减少（23-27%，p<0.01）。暴露于富含 UDCA 的“人工胆汁”的 HT-29 细胞的细胞生长减少（p<0.001），无论是在没有塞来昔布还是存在塞来昔布的情况下。在 LT97 细胞中孵育富含 UDCA 的“人工胆汁”时，仅在存在塞来昔布的情况下细胞生长才减少（p<0.05）。没有明确的证据表明增殖细胞核抗原、半胱天冬酶-3 或 COX-2 参与导致观察到的细胞生长变化的细胞过程。总之，低剂量塞来昔布和 UDCA 的联合治疗对源自 FAP 患者的结直肠腺瘤细胞具有生长抑制作用，需要进一步研究这种联合作为有前途的化学预防策略。
