探究五氟尿嘧啶（5-FU）联用VB2对其体内和体外抗结肠肿瘤活性的协同作用。体外，通过MTT和Chou-TalalayMethod法定量分析二者联用指数（CI）（CI=1加和作用；CI<1协同作用；CI>1拮抗作用）；采用Western blot、细胞流式研究联用对凋亡蛋白PARP切割以及细胞周期的影响。体内，以结肠癌Balb/c荷瘤小鼠实验探究两药联用对小鼠肿瘤生长和免疫生理功能的影响。结果显示，5-FU与VB2联用，C26细胞抑制率50%及90%时相应的CI值分别为0.52和0.13，具有协同效应。联用组较5-FU和VB2单用组的PARP蛋白切割条带增强显著，周期实验联用组G1期比例为75.12%较5-FU单用组64.02%明显提高，且差异具有统计学意义（p<0.05）。体内，5-FU与VB2联用后小鼠肿瘤抑制率从51.53%提高至76.18%，瘤体比指数从0.16下降为0.071，且差异均具有显著性（p<0.001）；脾脏指数联用组与5-FU单用组相比显著降低；肝肾指数以及血尿尿素氮和血浆肌酐含量各组并无统计学差异；与5-FU治疗组血浆尿酸含量108.50 μmol/L相比，联用组尿酸含量仅为59.75 μmol/L，显著下降（p<0.001）。因此，5-FU与VB2联用对结肠癌细胞C26和Balb/c荷瘤小鼠具有协同抗肿瘤活性，且与细胞G1期阻滞有关。

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.

国家自然科学基金资助项目（31773064）