Synergistic Tumor Inhibition Effects of Vitamin B2 and 5-fuorouracil on Colon Cancer Cell C26 and Balb/c Mice
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Abstract:
The aim of this research is toexplore the synergistic effect of penta-fluorouracil (5-FU) combined with VB2 on anti-colon tumor activity in vivo and in vitro. In vitro, the combined index (CI) was quantitatively analyzed by MTT assay and Chou-Talalay Method (CI=1 additive effect; CI<1 synergistic effect; CI>1 antagonism); the influence of drug combination on the cleavage of apoptotic protein PARP and cell cyclewas studied through cell flow and Western blot experiments. In vivo, the animal experiments of colon cancer Balb/c tumor-bearing mice were used to explore the effect of combining two drugs on tumor growth and immune function. The results showed that 5-FU combined with VB2, the corresponding CI values to 50% and 90% of C26 cell inhibition were 0.52 and 0.13 respectively, so the effect of these two drugs combination was synergistic. The PARP protein band was observed using 5-FU or VB2 alone, but the band of the combined group was significantly enhanced. Besides, the percentage in the G1 phase for thecombing drugs group was 75.12%, while the 5-FU group was 64.02%, and the difference was statistically significant (p<0.05). In vivo, after combining two drugs, the tumor inhibition rate of mice increased from 51.53% to 76.18%, and the tumor body ratio index decreased from 0.16 to 0.07, and the difference was significant (p<0.001); spleen index of combination group was obviously lower than 5-FU single-use group; liver and kidney index and blood urea nitrogen and plasma creatinine levels were not statistically different; and compared with the 5-FU treatment group (its plasma uric acid content was 108.50 μmol/L), the uric acid content of the combination group was only 59.75 μmol/L, which was significantly decreased (p<0.001). Therefore, 5-FU combined with VB2 has synergistic antitumor activity in colon cancer C26 cells and Balb/c tumor-bearing mice, and is associated with cell G1 arrest.
