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AIM To investigate the anticancer effect of a recombinant adenovirus-mediated p53(r Ad-p53) combined with 5-fluorouracil(5-FU) in human colon cancer resistant to 5-FU in vivo and the mechanism of r Ad-p53 in reversal of 5-FU resistance.METHODS nude mice bearing human colon cancer SW480/5-FU(5-FU resistant) were randomly assigned to four groups(n = 25 each): control group, 5-FU group, r Ad-p53 group, and r Ad-p53 + 5-FU group. At 24 h, 48 h, 72 h, 120 h and 168 h after treatment, 5 mice were randomly selected from each group and sacrificed using an overdose of anesthetics. The tumors were removed and the protein expressions of p53, protein kinase C(PKC), permeability-glycoprotein(P-gp) and multidrug resistance-associated protein 1(MRP1)(Western blot) and apoptosis(TUNEL) were determined.RESULTS The area ratios of tumor cell apoptosis were larger in the r Ad/p53 + 5-FU group than that in the control, 5-FU and r Ad/p53 groups(P < 0.05), and were larger in the r Ad/p53 group than that of the control group(P < 0.05) and the 5-FU group at more than 48 h(P < 0.05). The p53 expression was higher in the r Ad/p53 and the r Ad/p53 + 5-FU groups than that of the control and 5-FU groups(P < 0.05), and were higher in the r Ad/p53 + 5-FU group than that of the r Ad/p53 group(P < 0.05). Overexpression of PKC, P-gp and MRP1 was observed in the 5-FU and control groups. In the r Ad/p53 + 5-FU group, the expression of P-gp and MRP1 was lower that of the control and 5-FU groups(P < 0.05), and the expression of PKC was lower than that of the control, 5-FU and r Ad/p53 groups at more than 48 h(P < 0.05). In the r Ad/p53 group, the expression of P-gp and MRP1 was lower that of the control and 5-FU groups at more than 48 h(P < 0.05), and the expression of PKC was lower than that of the control and 5-FU groups at more than 120 h(P < 0.05).CONCLUSION5-FU combined with r Ad-p53 has a synergistic anticancer effect in SW480/5-FU(5-FU resistance), which contributes to reversal of 5-FU resistance.
AIM To investigate the anticancer effect of a recombinant adenovirus-mediated p53 (r Ad-p53) combined with 5-fluorouracil (5-FU) in human colon cancer resistant to 5-FU in vivo and the mechanism of r Ad-p53 in reversal of 5-FU resistance. METHODS nude mice bearing human colon cancer SW480 / 5-FU (5-FU resistant) were randomly assigned to four groups (n = 25 each) , and r Ad-p53 + 5-FU group. At 24 h, 48 h, 72 h, 120 h and 168 h after treatment, 5 mice were randomly selected from each group and sacrificed using an overdose of anesthetics. The tumors were removed and the protein expressions of p53, protein kinase C (PKC), permeability-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1) cell apoptosis were larger in the r Ad / p53 + 5-FU group than that in the control, 5-FU and r Ad / p53 groups (P <0.05), and were larger in the r Ad / p53 group than that of t The control group (P <0.05) and the 5-FU group at more than 48 h (P <0.05). The p53 expression was higher in the r Ad / p53 and the r Ad / p53 + 5- The control and 5-FU groups (P <0.05), and were higher in the rAd / p53 + 5-FU group than that of the Ad / p53 group (P <0.05). Overexpression of PKC, P-gp and MRP1 was observed in the 5-FU and control groups. In the rAd / p53 + 5-FU group, the expression of P-gp and MRP1 was lower that of the control and 5-FU groups (P <0.05), and The expression of PKC was lower than that of the control, 5-FU and r Ad / p53 groups at more than 48 h (P <0.05). In the r Ad / p53 group, the expression of P-gp and MRP1 was lower that of the control and 5-FU groups at more than 48 h (P <0.05), and the expression of PKC was lower than that of the control and 5-FU groups at more than 120 h (P <0.05) .CONCLUSION5- FU combined with r Ad-p53 has a synergistic anticancer effect in SW480 / 5-FU (5-FU resistance), which contributes to reversal of 5-FU resistance.