腺病毒介导p53基因联合肿瘤坏死因子对H22腹水瘤的协同作用

Synergic antitumor effect of combination of adenoviral-mediated p53 gene transfer and tumor necrosis factor in an H22 ascitic tumor-bearing mouse model

目的评价p53腺病毒注射液(AD-p53)与肿瘤坏死因子(TNF)联合腹腔给药对H22腹水瘤模型的协同抑制作用。方法建立H22腹水瘤的昆明小鼠模型,48 h后以AD-p53、TNF、生理盐水等腹腔注射,治疗周期为1周,治疗后测量腹围、体重,计量腹水,计数瘤细胞数,以流式细胞分析检测瘤细胞凋亡、死亡比例及细胞周期。结果AD-p53腹腔给药1周,出现瘤细胞G_0/G_1期阻滞；其和TNF联用后,未生成腹水的小鼠增多；在生成腹水的小鼠,腹水量和瘤细胞数均较单用时明显减少。结论AD-p53可阻滞瘤细胞周期,抑制增殖,联合TNF腹腔给药,在抑制腹水瘤时具有协同作用。

Objective To evaluate the synergic effects of intraperitoneal adenoviral p53 gene therapy together with tumor necrosis factor against H22 ascitic tumor-bearing mouse modeh Methods KM mouse model was established by intraperitoneal injection of H22 hepatic carcinoma. Forty-eight h after inoculation,adenoviral-mediated p53 gene was administrated intraperitoneally alone, or combined with tumor necrosis factor within 7 days. The abdominal girth, body weight, tumor cell number, apoptosis and cell cycle were tested using methods of cell counting and flow cytometry. Results Adenoviral p53 gene transfer alone arrested H22 cell in G0/G1. In combination therapy group, ascitic fluid was obviously halted, and tumor cells in peritoneal cavity were decreased in number and ascites formation. Conclusion Adenoviral-mediated p53 gene could block cell proliferation. Intraperitoneal adenoviral p53 gene therapy combined with tumor necrosis factor showed synergism for the inhibition for malignant ascites.