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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver metastasis is a major contributor to mortality in patients with colorectal cancer. Hence, it is essential to establish preventive therapy to control liver metastasis. Recently, it has become widely accepted that cyclooxygenase (COX)-2 inhibitors possess anti-cancer activity for various types of tumor, especially colorectal. The clinical application of COX-2 inhibitors may therefore be beneficial. In this study, we have developed a combined treatment with a selective COX-2 inhibitor and fluorinated pyrimidines for liver metastasis of colorectal cancer, and examined the effect of these agents on proliferation and invasion of a highly metastatic human colon cancer cell line, LM-H3. The COX-2 inhibitor etodolac was found to inhibit cell invasion of LM-H3. 5-Fluorouracil (5-FU) inhibited proliferation of this line in vitro. Etodolac did not increase the inhibitory effect of 5-FU on cell proliferation. We also examined the inhibitory effect of etodolac and UFT, belonging to the fluorinated pyrimidines, on liver metastasis by using a liver metastatic model in the nude mouse. Combined treatment with etodolac and UFT markedly reduced liver metastasis. Serious side effects were not observed. In conclusion, combined treatment with etodolac and UFT might be a promising preventive therapy for liver metastasis of colon cancer.
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PMID:Combined treatment with selective cyclooxygenase-2 inhibitor and fluorinated pyrimidines for liver metastasis of colon cancer. 1465 21

The cyclooxygenase-2 (COX-2) protein is highly expressed in a variety of human cancers and has been reported to promote tumor growth. Non-steroidal anti-inflammatory drugs such as etodolac and celecoxib have been shown to inhibit COX-2 activity and may play a role in the chemoprevention of cancer. Oxaliplatin is a third-generation platinum compound that exhibits a different spectrum of activity compared with cisplatin. Other cisplatin-resistant tumors can still respond to oxaliplatin. However, the anticancer ability of the combination of COX-2 inhibitors and oxaliplatin is still unknown. In this study, we investigated the effects of combination of COX-2 inhibitors and oxaliplatin on the cell growth and survival in human colon cancer cells. Treatments with etodolac (0.3-0.5 mM) or celecoxib (20-80 microM) for 24 h concentration-dependently induced the cytotoxicity in the RKO colon carcinoma cells. Etodolac and celecoxib did not alter the COX-2 protein levels but inhibited its enzyme activity to reduce prostaglandin E2 production. Furthermore, the cell survival was concentration-dependently decreased following oxaliplatin (1-100 microM, 24 h) treatment. Combination of oxaliplatin and etodolac additively increased the death and growth inhibition of RKO cells. Survivin, an inhibitor protein of apoptosis, mediates anti-apoptosis and promotes cell division in cancer cells. Oxaliplatin or COX-2 inhibitors significantly decreased the levels of survivin proteins. Moreover, survivin proteins were markedly diminished following co-treatment with oxaliplatin and etodolac. Together, this is the first report that combination of COX-2 inhibitors and oxaliplatin can increase the reduction of survivin protein expression, growth inhibition, and death in human colon cancer cells.
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PMID:Combination of cyclooxygenase-2 inhibitors and oxaliplatin increases the growth inhibition and death in human colon cancer cells. 1600 71