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塞来昔布与牛磺熊去氧胆酸联合治疗抑制家族性腺瘤性息肉病衍生 LT97 结肠腺瘤细胞的细胞生长。

Celecoxib and tauro-ursodeoxycholic acid co-treatment inhibits cell growth in familial adenomatous polyposis derived LT97 colon adenoma cells.

机构信息

Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

出版信息

Exp Cell Res. 2012 Apr 15;318(7):819-27. doi: 10.1016/j.yexcr.2012.02.004. Epub 2012 Feb 14.

Abstract

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.

摘要

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。

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