Efficacy of 5-fluorouracil and metronomic chemotherapy mediated ornithine decarboxylase antizyme for inhibiting of colorectal cancer.

the inhibitory therapy for colorectal cancer (CRC) is currently a hot topic in clinical research, and the stability between ornithine decarboxylase antienzyme (OAZ) and polyamine has a regulatory effect on normal cell growth. 5-fluorouracil (5-FU) can up-regulate the expression efficiency of OAZ. It was to explore molecular mechanism and expression of 5-FU-mediated OAZ inhibition of the development of CRC, and to compare the mediation effect of 5-FU and uracil, providing a research basis for CRC therapy. A CRC mouse model was established using the colon adenocarcinoma cell line CT-26. After successful modeling, 96 mice were randomly divided into three groups: the control group (CG) received saline as a placebo; group G1 received conventional 5-FU chemotherapy (20 mg/m2, 3 times per week); and group G2 received low-dose, continuously administered metronomic 5-FU chemotherapy (500 mg/m2, once daily). All treatments lasted for eight weeks. Initially, there were 32 mice per group. After treatment, 15 mice from each group were used to compare OAZ programmed ribosomal frameshifting expression activity, polyamine levels, tumor cell inhibitory effects, and adverse reactions (ARs). The remaining mice were maintained under standard housing conditions for continued observation until twelve weeks post-treatment to record long-term survival and tumor recurrence. After treatment, OAZ protein content was increased, and the OAZ protein content ((0.112 ± 0.0045), (0.143 ± 0.005)) and positive expression rate (88.96%, 90.23%) in groups G1 and G2 were higher than those in CG (0.069 ± 0.0035, 70.21%) (P < 0.05). The increase levels of OAZ (0.069 ± 0.0035) and OAZ programmed ribosomal frameshift (102 ± 10.61) in CG were lower than those in groups G1 and G2 (P < 0.05). Western blot and RT-qPCR results further demonstrated that, compared to the CG, the protein and mRNA expression levels of the OAZ downstream target ODC, as well as the ribosomal proteins RPL10 and RPS6, were significantly downregulated in both the groups G1 and G2 (all P < 0.05). After treatment, polyamine levels decreased in all three groups, but more dramatically in groups G1 and G2 than CG (P < 0.05). Furthermore, the total effective rate (TER)of Group G1 and Group G2 was much higher than that of CG (80%, 86.67% vs. 46.67%),and the TER of Group G2substantially surpassed that of Group G1 (P < 0.05).AR incidence in Group G2 (6.67%) was lower than that in Group G1 (46.67%) (P < 0.05).Long-term follow-up results indicated that the group G2 exhibited the longest median survival time and the lowest tumor recurrence rate. As a classical chemotherapeutic agent, 5-FU inhibits CRC progression by enhancing OAZ programmed ribosomal frameshifting efficiency and reducing intracellular polyamine levels. Compared with conventional chemotherapy, the metronomic 5-FU regimen demonstrated improved safety and efficacy in the preclinical model, with reduced toxic side effects, suggesting potentially superior patient tolerability and long-term prognosis.