荷载白介素24的溶瘤腺病毒联合达卡巴嗪对裸鼠黑素瘤的抑制作用

目的 研究荷载白介素24（IL-24）的溶瘤腺病毒ZD55-IL-24联合达卡巴嗪抑制裸鼠黑素瘤的作用。方法 建立裸鼠恶性黑素瘤A375细胞移植瘤模型后，分别给予ZD55-IL-24联合达卡巴嗪、ZD55-IL-24、达卡巴嗪、磷酸盐缓冲液（PBS）干预。Western印迹法检测A375细胞移植瘤组织IL-24、E1A蛋白表达。测量裸鼠肿瘤生长体积。结果 Western印迹结果表明，ZD55-IL-24联合达卡巴嗪作用的裸鼠黑素瘤高效表达IL-24、E1A蛋白。接种30 d后，ZD55-IL-24联合达卡巴嗪组肿瘤平均体积为（2346.5 ± 576.0） mm3，ZD55-IL-24组为（4141.6 ± 1348.2） mm3，达卡巴嗪组为（5230.1 ± 922.8） mm3，PBS组为（7135.1 ± 1002.3）mm3，ZD55-IL-24联合达卡巴嗪组与各组之间差异均有统计学意义（P ＜ 0.05）。结论 荷载IL-24基因的溶瘤腺病毒ZD55-IL-24联合达卡巴嗪有抑制黑素瘤增殖的作用。

Inhibitory effect of dacarbazine and an oncolytic adenovirus carrying interleukin-24 on transplanted melanoma in nude mice

Objective To investigate the inhibitory effect of dacarbazine and an oncolytic adenovirus carrying interleukin-24 （IL-24） on transplanted melanoma in nude mice. Methods Nude mice were inoculated with human A375 melanoma cells to establish a model of malignant melanoma. Then, the mice were divided into 4 groups to be treated with an oncolytic adenovirus carrying interleukin-24 （ZD55-IL-24）, dacarbazine, the combination of ZD55-IL-24 and dacarbazine, and phosphate buffer （PBS）, respectively, for 3 days. Seven days after the end of the treatment, some mice were sacrificed followed by the determination of IL-24 and E1A protein levels in tumor tissue by Western blot. The tumor volume was measured on a daily basis for 30 days. Results IL-24 and E1A were highly expressed in melanoma cell-bearing nude mice treated with ZD55-IL-24 and dacarbazine. At 30 days after the inoculation, the average volume of transplanted melanoma was （2346.5 ± 576.0） mm3 in the combination group, significantly different from that in the ZD55-IL-24 group （（4141.6 ± 1348.2） mm3, P < 0.05）, dacarbazine group （（5230.1 ± 922.8） mm3, P < 0.05）, and the control group （（7135.1 ± 1002.3） mm3, P < 0.05）. Conclusion The ZD55-IL-24 in combination with dacarbazine exhibits a remarkably inhibitory effect on the proliferation of melanoma transplanted into nude mice.