槲皮素对裸鼠肝癌切除术后肿瘤复发的影响及机制
Influence of Quercetin on the Recurrence of Tumor After Liver Cancer Resection in Athymic Mice and its Mechanism
-
摘要: 目的 体内实验研究槲皮素能否抑制裸鼠肝癌切除术后的肿瘤复发, 探讨其可能的分子机制.方法建立模拟人肝癌切除术后肿瘤高复发的裸鼠模型, 实验组裸鼠槲皮素75 mg/ (kg·d) 灌胃, 观察各组裸鼠复发情况, Western-blot检测其P65、MMP-2、E-Cadherin蛋白的表达.结果 槲皮素组校对照组肝内复发肿瘤体积减小[ (25.49±9.78) mm3vs (49.75±7.53) mm3, P<0.05], 复发灶数目减少[ (1.00±0.71) vs (2.20±0.84) , P<0.05].采用Western blot检测蛋白表达, 槲皮素组校对照组E-Cadherin表达增高[ (136.24±3.03) vs (144.70±5.02) , P<0.05], MMP-2蛋白表达下降[ (169.21±5.32) vs (158.17±4.80) , P<0.05], P65蛋白表达降低[ (170.07±6.61) vs (156.26±8.60) , P<0.05].结论 槲皮素能够抑制裸鼠肝癌术后肿瘤的复发, 其机制可能与槲皮素上调E-Cadherin的表达, 下调P65蛋白和MMP-2有关.Abstract: Objective To study the impact of quercetin on tumor recurrence after hepatectomy in athymic mouse hepatoma and the mechanism.Methods We established high-recurrent athymic mouse model simulating post-operation human HCC.For experimental group, we administered the mice with quercetin solution 75 mg/ (kg.d) by gavage, and observed tumor recurrence of the mice.Then we detected the expression of MMP-2, TIMP-2 in recurrent tumor using Western-blot.Results Compared with control group, mice in quercetin group had smaller liver recurrent focus volumn [ (25.49±9.78) mm3 VS (49.75±7.53) mm3, P<0.05) ], less liver recurrent focus[ (1.00±0.71) vs (2.20±0.84) , P<0.05].Western-blot was used to detect the expression of P65, MMP-2 and E-Cadherin.Compared with control group, the P65 and MMP-2 expression of the recurrent tumor in quercetin group decreased [ (170.07±6.61) vs (156.26±8.60) , P<0.05], [ (169.21±5.32) vs (158.17±4.80) , P<0.05], and the E-Cadherin expression in quercetin group increased [ (136.24±3.03) vs (144.70±5.02) , P<0.05].Conclusions Quercetin could restrain tumor recurrence in athymic mice after hepatectomy.The mechanism may be that quercetin could decrease the expression of P65 and MMP-2 and increase the expression of E-Cadherin in recurrent tumor.
-
Key words:
- Quercetin /
- Hepatectomy /
- Recurrence /
- P65 /
- MMP-2 /
- E-Cadherin
-
[1] [1]CHEN W Q, ZHENG R S, ZENG H M, et al.Annual report on status of cancer in China[J].Chin J Cancer Res, 2015, 27 (1) :2-12. [2] 汤钊猷.关于肝癌治疗的策略[J].临床肝胆病杂志, 2011, 27 (4) :337-339. [3]阿永俊, 李刚, 王志萍, 等.槲皮素对人肝癌高转移细胞人肝癌高转移细胞基质粘附能力的影响[J].昆明医科大学学报, 2015, 36 (5) :30-32. [4] [4]CHEN P, HU MD, DENG X F, et al.Genistein reinforces the inhibitory effect of cisplatin on liver cancer recurrence and metastasis after curative hepatectomy[J].Asian Pac J Cancer P, 2013, 14 (2) :759-764. [5] [5]CARNEIRO P, FIGUEIREDO J, BORDEIRA-CARRIO R, et al.Therapeutic targets associated to E-cadherin dysfunction in gastric cancer[J].Expert Opin Ther Targets, 2013, 17 (10) :1187-1201. [6] [6]CANEL M, SERRELS A, FRAME M C, et al.E-cadherin-integrin crosstalk in cancer invasion and metastasis[J].J Cell Sci, 2013, 126 (2) :393-401. [7] [7]LAI W W, HSU S C, CHUEH F S, et al.Quercetin inhibits migration and invasion of SAS human oral cancer cells through inhibition of NF-κB and matrix metalloproteinase-2/-9 signaling pathways[J].Anticancer Res, 2013, 33 (5) :1941-1950. [8] [8]YAMAD S, YANAMOTO S, NARUSE T, et al.Skp2 regulates the expression of MMP-2 and MMP-9 and enhances the invasion potential of oral squamous cell carcinoma[J].Pathol Oncol Res, 2016, 22 (3) :625-632. [9] [9]ZHANG Z X, LIU Z Q, JIANG B, et al.BRAF activated non-coding RNA (BANCER) promoting gastric cancer cells proliferation via regulation of NF-κB1[J].Biochem Biophys Res Commun, 2015, 465 (2) :225-231. [10] [10]KIMIO S, SATOSHI K, HIROAKI S, et al.Pin1 facilitates NF-κB activation and promotes tumour progression in human hepatocellular carcinoma[J].British Journal of Cancer, 2015, 113 (9) :1323-1331.
点击查看大图
计量
- 文章访问数: 1982
- HTML全文浏览量: 630
- PDF下载量: 119
- 被引次数: 0