Objective: To investigate the effect of acetyl-11-keto-β-boswellic acid(AKBA) on colorectal cancer xenografts in nude mice and its possible mechanism. Methods: The nude mouse models of colorectal cancer were established.Thirty cases of colorectal cancer models were divided into model group and AKBA group according to random number method, with 15 rats in each group. The nude mices in AKBA group were given AKBA intragastrically once a day(60 mg·kg-1)and the nude mices in model group were given the same amount of normal saline once a day, all for 3 weeks. The body weight and tumor volume of nude mice were measured daily. After 3 weeks, Hematoxylin-eosin(HE) staining were performed in nude mice xenografts. Immunohistochemistry method was used to determine the expression level of β-catenin protein in xenografts tissues. Western blotting method was used to determine the levels of cyclin D1, cytoplasmic proliferating antigen(PCNA), matrix metalloproteinase-2(MMP-2) and matrix metalloproteinase-7(MMP-7) in xenografts tissues. The mRNA levels of cyclin D1, PCNA, MMP-2 and MMP-7 mRNA in xenografts tissues were determined by reverse transcription-polymerase chain reaction (RT-PCR).Results: There was no significant difference in body weight between the two groups(P > 0.05).The volume of xenografts in the AKBA group was significantly smaller than that of the model group(P > 0.05). Obvious cell abnormalities were found in the xenografts in model group by HE staining method. In addition, the tumor cells in model group formed adenoid structures with irregularly arranged and varying sizes, and nuclear fission and microvasculars formation was common. However, the xenografts cell abnormalities was smaller in AKBA group, and adenoid structure was increased and the blood vessels was reduced. The positive expression rate of β-catenin in AKBA group was significantly lower than that in the model group(P < 0.05). The expression levels of cyclin D1,PCNA, MMP-2, MMP-7 protein and mRNA in the AKBA group were significantly lower than those in the model group(P < 0.05).Conclusion: AKBA can inhibit the growth of colorectal cancer xenografts via down-regulating Wnt/β-catenin signaling pathway in nude mice. |
[1] RONCUCCI L,MARIANI F.Prevention of colorectal cancer:how many tools do we have in our basket?[J].Eur J Intern Med,2015,26(10):752-756.
[2] HARALDSDOTTIR S,EINARSDOTTIR H M,SMARADOTTIR A,et al.Colorectal cancer-review[J].Laeknabladid,2014,100(2):75-82.
[3] 陆益彬,何明芳.乙酰基-11-酮-β-乳香酸抗肿瘤活性的研究进展[J].肿瘤研究与临床,2012,24(8):565-566.
[4] 蔡悠悠,夏媛媛,谷元,等.3-乙酰基-11-羰基-β-乳香酸在大鼠体内的代谢途径研究[J].中草药,2013,44(17):2427-2432.
[5] 袁小瑜,李跃辉,齐振华,等.乙酰基-11-酮基-β乳香酸对急性髓系白血病细胞HL-60细胞增殖、凋亡和细胞周期的影响[J].中国实验血液学杂志,2010,18(6):1440-1444.
[6] LIU H P,GAO Z H,CUI S X,et al.Chemoprevention of intestinal adenomatous polyposis by acetyl-11-keto-beta-boswellic acid in APC (Min/+) mice[J].Int J Cancer,2013,132(11):2667-2681.
[7] 柯晗昵,曲显俊.乙酰基-11-酮基-β-乳香酸与阿斯匹林对HCT-116作用的比较研究[J].中华肿瘤防治杂志,2015,22(2):103-108.
[8] YUAN Y,CUI S X,WANG Y,et al.Acetyl-11-keto-beta-boswellic acid (AKBA) prevents human colonic adenocarcinoma growth through modulation of multiple signaling pathways[J].Biochim Biophys Acta,2013,1830(10):4907-4016.
[9] KANG D W,LEE B H,SUH Y A,et al.Phospholipase D1 inhibition linked to upregulation of icat blocks colorectal cancer growth hyperactivated by wnt/β-catenin and PI3K/Akt signaling[J].Clin Cancer Res,2017,23(23):7340-7350.
[10] BAHRAMI A,AMERIZADEH F,SHAHIDSALES S,et al.Therapeutic potential of targeting Wnt/β-catenin pathway in treatment of colorectal cancer:rational and progress[J].J Cell Biochem,2017,118(8):1979-1983.
[11] PARK G H,SONG H M,KIM Y S,et al.Anti-cancer activity of Bacillus amyloliquefaciens AK-0 through cyclin D1 proteasomal degradation via GSK3β-dependent phosphorylation of threonine-286[J].Pharmazie,2017,72(6):348-354.
[12] ZHANG X,SUKAMPORN P,ZHANG S,et al.3,3'-diindolylmethane downregulates cyclin D1 through triggering endoplasmic reticulum stress in colorectal cancer cells[J].Oncol Rep,2017,38(1):569-574.
[13] ZUMWALT T J,WODARZ D,KOMAROVA N L,et al.Aspirin-induced chemoprevention and response kinetics are enhanced by PIK3CA mutations in colorectal cancer cells[J]. Cancer Prev Res (Phila),2017,10(3):208-218.
[14] KOSTOVA E,SLANINKA-MICESKA M,LABACEVSKI N,et al.Expression of matrix metalloproteinases 2,7 and 9 in patients with colorectal cancer[J].Vojnosanit Pregl,2014,71(1):52-59.
[15] 郭建霞,张小云,赵春林,等.Wnt/β-连环蛋白信号通路相关因子与结肠癌患者预后的相关性研究[J].河北医药,2016,38(3):371-373.
[16] 周玉涛,周中银,操寄望,等.小干扰RNA沉默β-连环蛋白基因对人结肠癌SW480细胞增殖及凋亡的影响[J].武汉大学学报(医学版),2015,36(2):231-234.
[17] WANG R,WANG Y,GAO Z,et al.The comparative study of acetyl-11-keto-beta-boswellic acid (AKBA) and aspirin in the prevention of intestinal adenomatous polyposis in APC (Min/+) mice[J].Drug Discov Ther,2014,8(1):25-32. |