腺病毒介导的血管抑素K1-5转基因治疗裸鼠卵巢癌移植瘤

Adenovirus Mediated Transfer of Angiostatin K1-5 gene Inhibits Nude Murine Ovarian Carcinoma

目的:探讨血管抑素k1-5对裸鼠卵巢癌皮下移植瘤的治疗作用。方法:20只荷瘤裸鼠随机分成4组,每组5只,DDP组:顺铂(DDP)20mg/kg,腹腔内注射隔日1次,连续5次;AdHA组:表达血管抑素k1-5基因的腺病毒载体(AdHA)1×108pfu/次,隔日1次,连续5次;AdHA+DDP组:AdHA1×108pfu/次,隔日1次,连续5次+DDP20mg/kg,腹腔内注射隔日1次,连续5次,以上3组为实验组。NS组(对照组):生理盐水(NS)100μL,腹腔内注射隔日1次,连续5次。以肿瘤体积、瘤质量及组织学改变来评价AdHA治疗效果及安全性。结果:瘤体内多点注射表达血管抑素k1-5的腺病毒能显著抑制肿瘤生长,AdHA组、DDP组及AdHA+DDP组较NS组肿瘤体积及瘤质量明显降低(P<0.05或P<0.01),且AdHA组及AdHA+DDP组较NS组微血管密度明显降低(P<0.05)。结论:表达血管抑素k1-5的腺病毒载体能抑制裸鼠卵巢癌皮下移植瘤的生长,且与化疗药联合应用有协同作用,提高肿瘤抑制率。

Objective： To evaluate therapeutic potential of angiostatin k1-5 for ovarian carcinoma of nude murine. Methods： Twenty nude murines with ovarian carcinoma were randomly divided into four groups which included DDP, AdHA, DDP＋AdHA and control group （NS） according to different drugs. The adenovirus expressing angiostatin k1-5 was used for treatment in nude murine with ovarian carcinoma in order to evaluate whether it could reduce the severity of ovarian carcinoma .Volume and weight of tumor as indexes were used for evaluating therapeutic effect. Results： Intratumor injection of adenovirus expressing angiostatin k1-5 significantly reduced both volume and weight of tumor （P 〈 0.05）. The clinical efficiency of this treatment was reflected by a reduction in MVD （P 〈 0.05）. AdHA＋DDP could significantly inhibit the growth of ovarian carcinoma of nude murine. Conclusions： Our experiment initially suggested that adenovirus mediated transfer of angiostatin k1-5 gene may be a good candidate to suppress nude routine ovarian carcinoma. Although we were unable to show complete disappear of ovarian cancer, a very significant degree reduction of volume and weight of tumor was observed in nude mice treated with adenovirus vector expressing angiostatin k1-5 gene.