△Np73基因沉默对结肠癌细胞5-氟尿嘧啶化疗敏感性的影响

Effect of △Np73 silencing on 5-FU chemotherapy sensitivity in colon cancer ceils

目的探讨小干扰RNA（siRNA）调节导致的△Np73抑制对结肠癌细胞SW6205-氟尿嘧啶（5-FU）药物敏感性的影响，为结肠癌治疗提供新途径。方法将△Np73 siRNA转染入SW620结肠癌细胞，观察其对结肠癌细胞△Np73表达的影响。并与5-FU联合使用，四甲基偶氮唑盐比色（MTT）法检测细胞活力，流式细胞技术检测细胞凋亡。分别将转染△Np73 siRNA和阴性对照siRNA的SW620细胞注射裸鼠成瘤，瘤中注射5-FU观察体内肿瘤的生长情况。结果△Np73 siRNA可显著抑制SW620结肠癌细胞△Np73的表达，但本身均不能抑制SW620结肠癌细胞的生长。同时应用△Np73 siRNA和5-FU共同处理的SW620细胞的凋亡率达到42．9％，显著高于单纯5-FU处理组（18．9％）和单纯△Np73处理组（8．8％）。在转染△Np73 siRNA的成瘤小鼠的瘤中注射5-FU，能明显抑制癌细胞体外生长（t=15．32，P〈0．05）。结论△Np73 siRNA可通过抑制△Np73的表达，从而增强对化疗药物的敏感性。

Objective To investigate the effect of small interfering RNA （siRNA） mediated silencing of △Np73 on 5-FU chemotherapy sensitivity in SW620 colon cancer cells and provide new treatment approach for the colon cancer. Methods siRNAs were transfected into SW620 colon cancer ceils. The expression of △Np73 was observed. Cell viability of colon cancer cells were measured by MTr assay and cell apoptosis was assessed with flow cytometry after treatment of control siRNA or △Np73 siRNA or combined with 5-FU, respectively. The tumorigenesis was assessed by injecting △Np73 siRNA or control siRNA transfected SW620 colon cancer cells into nude mice, followed by treatment with 5-FU in the tumors. Results △Np73 siRNA was able to strongly inhibit △Np73 expression, however, it did not inhibit the growth of cells. Combination treatment with △Np73 siRNA and 5-FU produced significant higher apoptotic cell（42. 9% ） as compared with those with 5-FU treatment（ 18.9% ） alone or those with △Np73 siRNA（8.8% ） alone. The treatment with 5-FU in the xenografts derived from △Np73 siRNA transfeeted SW620 ceils in nude mice can inhibitor tumor growth significantly （ t = 15.32, P 〈 0. 05 ）. Conclusion △Np73siRNAs can specifically repress the expression of △Np73. Thus it sensitizess the cells to 5-FU chemotherapy in colon cancer.