An in vivo study on the effect of oncolytic adenovirus CNHK600-IL24 on breast cancer / 中华普通外科杂志

ABSTRACT

Objective To construct an oncolytic adenovirus CNHK600-IL24, and to observe the in vivo effects of CNHK600-IL24 in treating breast cancer. Methods The IL-24 gene was cloned into adenovirus shuttle vector SG502-△CR2, and CNHK600-IL24 was obtained by cotransfection of SG502-INSIL24 and pPE3 plasmids and subsequent recombination in 293 cells. Based on the establishment of the athymic mice model of breast cancer in situ and imitated metastatic breast cancer by injection in the vena caudalis and the left artrium, we administered the virus by the tail vein. We used the optical imaging in vivo system to monitor the effects. Results The oncolytic adenovirus CNHK600-IL24 was correctly constructed and confirmed by restriction DNA sequence analysis and PCR. The titer of CNHK600-IL24 reached 1.9 ×1010pfu/ml. Establishing athymic mice model of breast cancer in situ, the volume and photon number of the tumors in the control group was significantly larger than those of the CNHK600-IL24 group( P ＜0. 05). The tumor had conspicuous necrosis after the treatment of CNHK600-IL24. There was noticeable apoptosis of the tumor cells. Immunohistochemistry showed the expression of IL-24 and the Hexon protein in the tumor cells.In athymic mice model of imitated metastatic breast cancer by infusion into the vena caudalis, most of the mice in the control group died before 38 days, the mice of the CNHK600-IL24 group survived significantly longer(P ＜0. 05 ). Using athymic mice model of imitated metastatic breast cancer by infusion in the left artrium, the optical imaging in vivo system showed obvious difference between the control group and the CNHK600-IL24 group. Conclusions The high-titer oncolytic adenovirus CNHK600-IL24 was successfully constructed and purified. The oncolytic adenovirus had obvious antitumor effect on breast cancer.