Abstract:
:The oral fluoropyrimidine S-1 has marked efficacy in treating metastatic colorectal cancer patients. In the present study, we explored the therapeutic potential of combined in vivo treatment in the human colon cancer cell lines COL-1, KM12C and KM20C with consecutive oral S-1 and leucovorin (LV) in 2-week therapeutic periods. This combination had increased anticancer activity compared to S-1 alone in the xenografts tested. Moreover, oral S-1/LV treatment showed a more potent anticancer effect on COL-1 xenografts than infusional 5-fluorouracil (5-FU)/LV, with comparable loss of body weight. The reduced folate level in the tumors was initially low, but rapidly rose and persisted for a long period of over 24 h after a single LV administration. This resulted in the formation of much higher levels of the ternary complex with thymidylate synthase (TS) and 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP) derived from 5-FU, leading to a prolonged inhibition of TS activity in combined administration with oral S-1. These results suggest that the co-administration of LV with S-1 might improve therapeutic efficacy in the treatment of colorectal cancer patients.
journal_name
Mol Med Repjournal_title
Molecular medicine reportsauthors
Tsukioka S,Uchida J,Tsujimoto H,Nakagawa F,Sugimoto Y,Oka T,Kiniwa Mdoi
10.3892/mmr_00000111subject
Has Abstractpub_date
2009-05-01 00:00:00pages
393-8issue
3eissn
1791-2997issn
1791-3004journal_volume
2pub_type
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