白藜芦醇对小鼠移植宫颈癌的抑制作用及机制研究

Inhibitory effect and mechanism of resveratrol on transplanted cervix cancer in mice

背景与目的:白藜芦醇(resveratrol,Res)是天然存在于葡萄等植物中的一种多酚类化合物,具有抗癌、抗氧化等作用。体外研究发现Res可抑制宫颈癌细胞的生长,但在体内是否有作用尚未见报道。本研究观察Res对小鼠宫颈癌细胞株U14移植瘤的抑制作用,并初步探讨Res的抗肿瘤作用机制。方法:建立615近交系小鼠U14移植瘤动物模型,并随机分成4组:对照组(0.9%的NaCl溶液)、Res低剂量组(每日剂量2.5 mg/kg)、Res高剂量组(每日剂量10 mg/kg)和顺铂组,每组10只。连续给药20 d,于接种后第26天处死小鼠,检测肿瘤体积及质量,计算抑瘤率,采用RT-PCR和Western blot分析肿瘤组织巨噬细胞移动抑制因子(migrationinhibitory factor,MIF)的表达水平,通过免疫组织化学法检测肿瘤组织微血管密度(microvesseldensity,MVD),并用原位末端标记法(TUNEL)检测肿瘤细胞凋亡指数(apoptosis index,AI)。结果:Res高剂量组、顺铂组肿瘤的生长明显受到抑制,肿瘤体积缩小,肿瘤质量明显低于对照组(P<0.01);Res高剂量组和顺铂组抑瘤率分别为52.94%、56.44%,明显高于Res低剂量组(P<0.01)。Res高剂量组和顺铂组MIF mRNA与蛋白表达水平及MVD明显降低,AI则明显升高,与对照组相比,差异均有统计学意义(P<0.01),但低剂量Res对MIF表达、MVD及AI无明显影响(P>0.05)。结论:Res可明显抑制小鼠宫颈癌的生长,机制可能与抑制MIF表达、降低MVD和促进细胞凋亡有关。

Background and purpose：Resveratrol（Res）,as a polyphenolic compound,is naturally enriched in plants such as grapes,which have been reported to have potent anticancer and antioxidant properties.In vitro studies have discovered that Res can inhibit cell growth of cervix cancer;however,there are no reports regarding the in vivo effects of Res on cervical cancer.The aim of this study was to observe the inhibitory effect of Res on transplanted cervical cancer cell U14 in mice,and to explore its mechanism.Methods：The 615-strain mice with U14 cervical cancer cells were randomly divided into 4 groups： control group（physiological saline）,Res low-dose group（2.5 mg/kg per day）,Res high-dose group（10 mg/kg per day） and cisplatin（DDP） group.Different treatments were administered starting from day 6 after transplantation.All mice were disposed of after 26 days.The volume and weight of all tumors were detected,and tumor inhibition rates were calculated.The expression levels of the macrophage migration inhibitory factor（MIF） mRNA and protein were all measured by RT-PCR and Western blot,respectively.Microvessel density（MVD） was measured by immunohistochemistry.Apoptosis index（AI） was determined by TUNEL assay.Results：Tumor growth was suppressed significantly in Res high-dose group and DDP group.The weight and volume of the tumors were markedly decreased in those groups than the control group（P0.01）.The tumor inhibition rates of the Res high-dose group and DDP group were 52.94% and 56.44%,respectively,which was higher than the rates in the Res low-dose group（P0.01）.The expression levels of MIF mRNA,protein and MVD were significantly lower in Res high-dose group and DDP group than those in control group（P0.01）.AI was enhanced in the Res high-dose group and DDP group in comparison with the control group.However,low-dose Res had no obvious influence on MIF expression,MVD and AI（P0.05）.Conclusion：Res can remarkably inhibit cervical cancer growth in mice,which may be due to an association with the inhibited expression of MIF,reducing MVD and promoting apoptosis.