ABSTRACT
Objective To investigate the effect of human epidermal growth factor receptor-2 (HER2) silenced by lentivirus-mediated RNA interference (RNAi) on the growth of SKOV-3 ovarian cancer,and to explore the value of radioimmunoimaging in monitoring the biotherapy of RNAi.Methods The ovarian cancer cell line SKOV-3 was infected with lentivirus-mediated HER2-short hairpin (sh) RNA expression vector and scrambled control lentivirus vector,respectively.Both infected cells were inoculated into nude mice to establish two ovarian cancer xenograft models:knock down 1 (KD1) group and normal control (NC) group.The uninfected SKOV-3 xenograft model served as blank control (CON) group.The tumor formation rate,tumor generation time and tumor size at different time points were measured.The expression of HER2 protein was measured by immunohistochemistry.1n Ⅰ-Herceptin was injected before radioimmunoimaging,and the T/B ratios were acquired.One-way analysis of variance and the least significant difference (LSD)-t test were performed with SPSS 17.0.Results All mice models were constructed successfully (100％,15/15).The average time of tumor generation was (4.583±0.520) d,(4.567±0.284) d and (6.023±0.316) d in CON,NC and KD1 groups,respectively(F=13.946,P＜0.01).The tumor formation time of KD1 group was significantly longer than the other two groups (t=4.557,4.608,both P＜0.01),respectively.On the 28th day after the tumor cell implantation,the tumor size was significantly different among the three groups (F=26.343,P＜0.01).The tumor mass was (0.614±0.135) g,(0.558±0.190) g and (0.120±0.489) g in CON,NC and KD1 groups,respectively (F=225.026,P＜0.01).Both the tumor size (t=7.125,4.759) and tumor mass (t=19.158,16.977) of KD1 group were significantly less than those of CON and NC groups (all P＜0.01),respectively.Immunohistochemical results showed that the HER2 protein expression was inhibited in the KD1 group.The tumor could be visualized clearly on radioimmunoimaging at different time points.The T/B ratio of the KD1 group (0.208-4.427) was significantly lower than those of the other two groups at any intervals (0.576-5.508,0.640-5.695; F=9.197-39.375,all P＜0.05).Conclusions The growth of SKOV-3 could be inhibited remarkably by lentivirus-mediated HER2-siRNA.Radioimmunoimaging with 1nI-Herceptin might positively correlate with the expression of HER2 protein,which might have potential for monitoring the biotherapy of RNAi targeting HER2.