Inhibitory Effects of Quercetin in Combined with Resveratrol on Growth of Lewis Lung Cancer in Mice
-
摘要: 目的 观察槲皮素联合白藜芦醇对小鼠Lewis肺癌细胞生长的作用及机制。方法建立C57BL/6小鼠Lewis肺癌移植瘤模型,随机分为对照组、槲皮素组、白藜芦醇组和联合用药组,每组10只,连续用药20天,于接种后第24天处死全部小鼠,比较各组肿瘤体积、肿瘤质量和抑瘤率,并用免疫组织化学、Western blot、TUNEL分别检测血管内皮生长因子 (VEGF)、基质金属蛋白酶-2(MMP-2)表达及凋亡指数(AI)。结果各用药组肿瘤的生长明显受到抑制,肿瘤体积和肿瘤质量明显低于对照组(P<0.05或0.01),联合用药组较单独用药组抑瘤作用显著增强(P<0.05)。各用药组较对照组VEGF、MMP-2表达降低(P<0.05或0.01),AI升高(P<0.05或0.01)。与单独用药组比较,联合用药组VEGF、MMP-2表达下调,AI升高,差异均有统计学意义(P<0.01)。结论槲皮素联合白藜芦醇对小鼠Lewis肺癌细胞生长具有明显的抑制作用,其机制可能与下调VEGF和MMP-2表达、促进细胞凋亡有关。Abstract: Objective To explore the inhibitory effects and mechanism of quercetin plus resveratrol on the growth of lewis lung cancer in mice. Methods Forty C57BL/6 mice with transplanted Lewis lung cancer were randomly divided into 4 groups with 10 mice in each group:control group,quercetin group,resveratrol group and combined group.Different treatments were served from day 4 and all mice were sacrificed on day 24 after transplantation.Tumor volume,weight and inhibitory rate were compared among the 4 groups.The expression levels of vascular endothelial growth factor(VEGF),matrix metalloproteinare-2(MMP-2) and apoptosis index(AI) were detected by immunohistochemistry,western blot and TUNEL,respectively. Results Tumor growth was significantly inhibited in drug-treated groups.Tumor volume and weight in drug-treated groups was lower than that of the control group(P<0.05 or 0.01).The anti-tumor efficacy of quercetin plus resveratrol was significantly higher compared with quercetin or resveratrol alone(P<0.05).Expression levels of VEGF and MMP-2 were decreased in drug-treated groups compared with the control group(P<0.05 or 0.01).AI increased in drug-treated groups compared with the control group(P<0.05 or 0.01).There was significant difference in the VEGF and MMP-2 expression as well as AI between combined group and drug-treated alone group(P<0.01). Conclusion Quercetin in combination with resveratrol had a strong inhibitory effect on the growth of lung cancer which might be related to the down-regulation of VEGF and MMP-2 and as well as the induction of cell apoptosis.
-
Key words:
- Lung cancer /
- Quercetin /
- Resveratrol /
- Vascular endothelial growth factor /
- Matrix metalloproteinare-2
-
-
[1] Sève P,Dumontet C.Chemoresistance in non-small cell lung cancer[J].Curr Med Chem AnticancerAgents,2005,5(1):73-88. [2] Murakami A,Ashida H,Terao J.Multitargeted cancer prevention by quercetin[J].CancerLett,2008,269(2):315-25. [3] Weng CJ,Yang YT,Ho CT,et al.Mechanisms of apoptotic effects induced byresveratrol,dibenzoylmethane,and their analogues on human lung carcinoma cells[J].J Agric FoodChem,2009,57(12):5235-43. [4] Long QD,Xiong SQ,Zhao X.Research progress of quercetin chemical prevention of cancer and antitumor function[J].Zhonghua Fu You Lin Chuang Yi Xue Za Zhi(Dian Zi Ban),2008,4(4):56-9.[龙奇达,熊绍权,赵霞.槲皮素的癌化学预防和抗肿瘤作用研究进展[J].中华妇幼临床医学杂志(电子版),2008,4(4):56-9.] [5] Hu LY,Wang HN,Pei JJ,et al.Research progress of resveratrol anticancer action and molecular mechanism[J].Shandong YiYao,2010,50(s):111-2.[胡凌云,王海钠,裴俊俊,等.白藜芦醇防癌抗癌作用及其分子机制研究进展[J].山东医药,2010,50(5):111-2.] [6] Mulkeen AL,Silva T,Yoo PS,et al.Short interfering RNA mediated gene silencing of vascularendothelial growth factor:Effects on cellular proliferation in colon cancer cells[J].ArchSurg,2006,141(4):367-74. [7] Uzzan B,Nicolas P,Cucherat M,et al.Microvessel density as a prognostic factor in women withbreast cancer:A systematic review of the literature and meta analysis[J].Cancer Res,2004,64(9):2941-55. [8] Li HM,Fang WG,Zheng J,et al.Zymographic analysis of MMPs in human carcinoma cell lines withdifferent metastasis potential[J].Zhonghua Bing Li Xue Za Zhi,1998,27(5):341-3.[李红梅,方伟岗,郑杰,等.不同转移潜能的人肿瘤细胞系金属蛋白酶活性分析[J].中华病理学杂志,1998,27( 5):341-3.] [9] Liu XZ,Song Z.The expression and its clinical significance of MMP-2 and NM23 in the tissues from non-small cell lung cancer and paracancerous tissues[J].Shi Yong Ai Zheng Za Zhi,2010,25(3):2000-2.[刘旭之,宋卓.MMP-2、NM23在非小细胞肺癌组织和癌旁组织中表达及其临床意义[J].实用癌症杂志,2010,25(3):2000-2.] [10] Feng Y,Tian Z,Wan M.Bioeffects of Low-Intensity Ultrasound In Vitro:Apoptosis,Protein ProfileAlteration,and Potential Molecular Mechanism[J].J Ultrasound Med,2010,29(6):963-74.
计量
- 文章访问数: 2679
- HTML全文浏览量: 20
- PDF下载量: 731
下载:
