熊果酸对人卵巢癌耐药SKOV3/DDP裸鼠移植瘤的抑制作用

Inhibitory Effect of Ursolic Acid on Drug-resistant SKOV3/DDP Ovarian Carcinoma Xenografts in Nude Mice

目的观察熊果酸对人卵巢癌耐顺铂SKOV3/DDP裸鼠移植瘤生长的影响,探讨其作用途径。方法建立人卵巢癌耐顺铂SKOV3/DDP细胞裸鼠异位移植瘤模型,将24只荷瘤鼠随机分为4组:空白对照(0.9%氯化钠溶液)组、顺铂(4 mg·kg-1·d-1)组和熊果酸小剂量(30 mg·kg-1·d-1)、大剂量(60 mg·kg-1·d-1)组,每组6只。腹腔注射给药,注射量均为10 m L·kg-1,每天1次,共15 d。给药后每3 d测量肿瘤体积,并绘制移植瘤生长曲线,计算各组抑瘤率,采用逆转录-聚合酶链反应(RT-PCR)、Western blotting法分别检测肿瘤组织Bcl-2、Bax mRNA及其蛋白表达水平。结果顺铂组和熊果酸小剂量、大剂量组抑瘤率分别为33.3%,43.4%,71.0%。移植瘤中Bcl-2表达均有下降,而Bax表达上调。结论熊果酸对人卵巢癌耐顺铂SKOV3/DDP细胞裸鼠移植瘤具有一定的抗瘤活性,可抑制瘤体生长,并呈现浓度依赖性,其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 explore the effects and mechanisms of ursolic acid on drug-resistant SKOV3/DDP ovarian carcinoma xenografts in nude mice. Methods The models of drug-resistant SKOV3/DDP ovarian carcinoma on athymic mouse were established and randomly divided into four groups with intraperitoneal injection of different drugs： blank control（ 0. 9%sodium chloride solution）,cisplatin（ 4 mg·kg^-1·d^-1）,ursolic acid low dose（ 30 mg·kg^-1·d^-1）,and high dose（ 60 mg·kg^-1·d^-1）. All drugs were injected at volumes of 10 m L·kg^-1perday for 15 days. The tumor volumes were measured during the process of drug treatment every three days. After 14 days,The tumorigenic rate and tumor inhibition rate were calculated. RT-PCR and Western blotting were performed to detect the expression of Bcl-2 and Bax. Results Anti-tumor rates of cisplatin group,low dose ursolic acid group,and high dose ursolic acid group was 33. 3%,43. 3%,and 71. 0%,respectively. Bcl-2 expressions were down-regulated,while Bax expressions were up-regulated in all three groups. Conclusion Ursolic acid has some anti-tumor activity on cisplatin-resistant human ovarian cancer SKOV3/DDP cell in nude mice. It can inhibit tumor growth with dose-effect relationship. The mechanism may be to suppress the expression of anti-apoptotic factor Bcl-2 and to increase the expression of apoptosis-promoting factors Bax.