Combined treatment with selective cyclooxygenase-2 inhibitor and fluorinated pyrimidines for liver metastasis of colon cancer.
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.
Matsunaga
Nobuo
N
Department of Surgical Oncology, Osaka City University, Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
Yamada
Nobuya
N
Ohira
Masaichi
M
Tachimori
Akiko
A
Nishiguchi
Yukio
Y
Nishino
Hiroji
H
Seki
Syuichi
S
Hirakawa
Kosei
K
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D017308:Etodolac / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D011451:Prostaglandin-Endoperoxide Synthases; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D017308:Etodolac; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D005472:Fluorouracil