Inhibitory effects of angiostatin gene combined with antisense hypoxia inducible factor-1? gene transfection on implanted human ovarian carcinoma in nude mice / 中国肿瘤生物治疗杂志

ABSTRACT

Objective: To observe the synergistic inhibitory effect of angiostatin gene combined with antisense hypoxia inducible factor-1? (aHIF-1?) gene on implanted human ovarian carcinoma in nude mice. Methods: BALB/C nude mice were subcutaneously transplanted with SKOV3 tumor cells and the tumors were allowed to grow till the diameter reached 0.4 cm, then the mice were randomly divided into 4 groups PcDNA3 control group, PcDNA3-Angiostatin group, PcDNA3B-aHIF-1? group and PcDNA3-Angiostatin+PcDNA3B-aHIF-1? group; plamids PcDNA3, PcDNA3-Angiostatin, PcDNA3B-aHIF-1? and PcDNA3-Angiostatin+PcDNA3B-aHIF-1? were injected intra-tumorally in the above groups, respectively. The tumor samples were harvested on the 7 th day after gene transfer. Angiostatin, HIF-1?, vascular endothelial growth factor (VEGF) and microvessel density (MVD) of tumors were determined by immunohistochemical methods. Tumor cell apoptosis was determined with TUNEL staining. Results:The growth of tumors of PcDNA3-Angiostatin+PcDNA3B-aHIF-1? group was significantly inhibited, with local low expression of HIF-1? and VEGF (lower than those of the other 3 groups). MVD in combined transfection group(13.6?2.3) was lower than that of Angiostain group (24.5?2.7); the apoptosis index in combined transfection group (5.32?0.62)was higher than those of Angiostatin group(2.89?0.45), aHIF-1? group(2.98?0.51)and contrl group(1.56?0.41). Conclusion: Our results suggest a synergestic effect between Angiostain gene and aHIF-1? gene in inhibiting implanted human ovarian tumors in nude mice, which may contribute to drug resistance in antiangiogenic therapy of tumors.