橄榄苦苷对卵巢癌裸鼠皮下移植瘤抑瘤作用的研究

Study on antitumor effects of oleuropein on ovarian cancer subcutaneous transplanted tumor in nude mice

目的观察橄榄苦苷对卵巢癌SKOV3裸鼠皮下移植瘤生长的影响,探讨其作用机制。方法建立卵巢癌SKOV3细胞裸鼠皮下移植瘤的模型,将20只荷瘤裸鼠随机分为2组,橄榄苦苷组:50 mg/(kg·d),按10 mL/kg腹腔内注射;等渗盐水组:按0.9%氯化钠注射液10 mL/kg腹腔内注射。2组均隔天给药1次,连续给药8周,自由摄水和进食,标准SPF饲养。每周测量裸鼠体重和肿瘤体积各1次。处死裸鼠后,完整分离出肿瘤组织,计算肿瘤的相对增殖率,采用Western blot法分别检测2组肿瘤组织促凋亡因子Bax、抗凋亡因子Bcl-2的表达水平。结果橄榄苦苷组裸鼠在注射药物后21 d、35 d、56 d的移植瘤体积明显小于等渗盐水组(P<0.01);橄榄苦苷组的相对肿瘤增殖率为70.3%;与等渗盐水组比较,橄榄苦苷组Bcl-2蛋白表达下调,而Bax蛋白表达上调。结论橄榄苦苷对卵巢癌SKOV3裸鼠皮下移植瘤的生长有抑制作用,机制可能与抑制抗凋亡因子Bcl-2的表达,增强凋亡促进因子Bax的表达有关。

Objective To observe the effects of oleuropein on the growth of subcutaneously transplanted ovarian cancer SKOV3 in nude mice and to explore its mechanism. Methods Established subcutaneous xenograft model of ovarian cancer SKOV3 cells.Twenty nude mice were randomly divided into two groups.Oleuropein group:50 mg/(kg·d),10 mL/kg intraperitoneally,saline group:0.9%sodium chloride injection 10 mL/kg intraperitoneal injection.Both groups were administered once every other day for 8 weeks,free water intake,and standard SPF feed.The tumor volume and body weight of nude mice were measured and recorded once a week.After the nude mice were sacrificed,the tumor tissues were completely isolated and the relative proliferation rate of the tumors was calculated.Western blot was utilized to detect the expression levels of pro-apoptosis factor Bax and anti-apoptosis factor Bcl-2 in the two groups of tumor tissues. Results The tumor volume of oleuropein group in nude mice at 21 days,35 days and 56 days after injection was significantly smaller than that of saline group(P<0.01);the relative tumor proliferation rate of oleuropein group was 70.3%;compared with saline group,oleuropein group Bax protein expression was up-regulated while Bcl-2 protein expression was down-regulated. Conclusion Oleuropein inhibits the growth of ovarian cancer SKOV3 cells subcutaneous transplanted tumor in nude mice.The mechanism may be related to inhibiting the expression of anti-apoptosis factor Bcl-2 and enhancing the expression of apoptosis-promoting factor Bax.