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

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• 作者：Bjorn W.H. van Heumen^a ; ^{b.vanheumen@mdl.umcn.nl} ; Hennie M.J. Roelofs^a ; René ; H.M. te Morsche^a ; Brigitte Marian^b ; Fokko M. Nagengast^a ; Wilbert H.M. Peters^a
• 关键词：APC ; adenomatous polyposis coli ; b2M ; Beta-2 microglobulin ; COX ; cyclooxygenase ; DMEM ; Dulbecco's Modified Eagle Medium ; DMSO ; dimethyl sulfoxide ; FAP ; familial adenomatous polyposis ; FBS ; fetal bovine serum ; NSAIDs ; non-steroidal anti-inflammatory drugs
• 刊名：Experimental Cell Research
• 出版年：2012
• 期刊代码：292_00144827
• 类别：med
• 出版时间：15 April, 2012
• 卷：318
• 期：7
• 页码：819-827
• 文件大小：1406 K

摘要

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 鈥榓rtificial bile鈥?enriched with UDCA, was decreased (p < 0.001), either in the absence or presence of celecoxib. In LT97 cells incubated with 鈥榓rtificial bile鈥?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.