增殖性溶瘤腺病毒ZD55-IL-24是靶向p53缺失且携带肿瘤特异性的白细胞介素-24基因(IL-24);丝裂霉素(mitomycin C,MMC)是一种目前临床上癌症治疗常用化疗药物之一。研究联合应用ZD55-IL-24和MMC与单独使用对肝癌细胞株的杀伤效应及机制。结果表明,ZD55-IL-24比携带对照基因EGFP的腺病毒ZD55-EGFP对肝癌细胞具有更强的杀伤效果,而联合使用ZD55-IL-24与MMC比单独使用对肝癌细胞具更好的治疗作用,而对正常细胞的损伤仅来源于化疗药物MMC。此外,Hoechst33258染色和Westernblot实验证明ZD55-IL-24与MMC联合处理诱导活化了肿瘤细胞的凋亡途径。以上结果显示肿瘤的传统疗法与新兴生物疗法相结合取得了更佳效果,本研究为临床肿瘤治疗提供理论和实验依据。
ZD55-IL-24 is a replicative oncolyitc adenovirus carrying tumor-specific interleukin-24 gene and targeting tumor cells with loss of p53. Mitomycin C (MMC) is one of most common chemical drugs in the clinical cancer therapy. Herein the authors have combined the ZD55-IL-24 and MMC and studied their killing effect and the mechanism by the combinational therapy or any single in hepatocellular carcinoma. The results indicate that ZD55-IL-24 exhibites stronger antitumor effect in liver cancer cells than that control virus ZD55-EGFP carrying the EGFP gene. Meanwhile, the combination with ZD55-IL-24 and MMC show the most killing efficacy than that of ZD55-IL-24 or MMC and their toxicity to normal cells is only caused by chemical drug MMC. Moreover, Hoechst33258 staining and western blot analysis have proved that the antitumor effect by the combined treatment is due to tumor cell apoptosis by the activation of cell apoptosis pathway mediated with MMC and IL-24 gene expression. In conclusion, the better antitumor activity by the combination with tumor traditional therapy and novel biotherapy offers the theoretic and research basis for the clinical tumor therapy.