红树莓根茎水煎剂对S180荷瘤小鼠肿瘤组织中C-myc、Cath-D表达的影响
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摘要
目的:探讨红树莓根茎水煎剂(RRD)对S180荷瘤小鼠核蛋白类调控基因(C-myc)、组织蛋白酶D(Cath-D)在肿瘤组织中表达的影响,分析RRD的抗肿瘤作用。方法:取40只清洁级ICR健康昆明(KM)种小鼠,雌性和雄性各占一半,随机分为4组,模型组、中药组(RRD)、环磷酰胺组(CTX)及联合用药组(RRD+CTX),每组10只,在腋下位置皮下接种S180瘤株细胞悬液0.2 mL造模。24 h后开始给药,模型组:生理盐水灌胃每天0.02 mL/g;RRD组:RRD灌胃每天0.4 mL/20 g;CTX组:生理盐水灌胃每天0.4 mL/20 g,腹腔注射CTX每天20 mg/kg;RRD+CTX组:RRD灌胃每天0.4 mL/20 g,腹腔注射每天CTX 20 mg/kg,1次/d,连续10 d。用免疫组化法检测肿瘤组织C-myc、Cath-D表达含量。结果:RRD能够使S180荷瘤小鼠肿瘤组织C-myc、Cath-D表达明显下降,且与模型组比较,差异有统计学意义(P<0.05)。结论:RRD对S180荷瘤小鼠的肿瘤抑制作用可能与抑制肿瘤增殖、侵袭和转移相关蛋白C-myc、Cath-D的表达有关。
Objective: To investigate the effects of RRD on the expression of nuclear protein regulatory genes(C-myc) and cathepsin D(Cath-D) in tumor tissues of S180 tumor-bearing mice, and to analyze the anti-tumor effect of RRD. Methods: Forty clean ICR healthy Kunming(KM) mice were randomly divided into four groups: model group, traditional Chinese medicine group(RRD), cyclophosphamide group(CTX) and combined drug group(RRD + CTX). Ten mice in each group were subcutaneously inoculated with S180 cell suspension at the axillary position to establish the model. After 24 h, the model group was given orally 0.02 mL/g/d with normal saline; RRD group was given orally 0.4 mL/20 g/d with RRD; CTX group was given orally 0.4 mL/20 g/d with normal saline and intraperitoneally 20 mg/kg/d with CTX; RRD+CTX group was given orally 0.4 mL/20 g/d with RRD and intraperitoneally 20 mg/kg/d with CTX once a day for 10 d. The expression of C-myc and Cath-D in tumor tissues was detected by immunohistochemistry. Results: RRD could significantly decrease the expression of C-myc and Cath-D in the tumor tissues of S180 tumor-bearing mice, and there was a significant difference between RRD and model group(P<0.05). Conclusion: The inhibitory effect of RRD on S180 tumor-bearing mice may be related to the inhibition of the expression of C-myc and Cath-D related proteins in tumor proliferation, invasion and metastasis.
Objective: To investigate the effects of RRD on the expression of nuclear protein regulatory genes(C-myc) and cathepsin D(Cath-D) in tumor tissues of S180 tumor-bearing mice, and to analyze the anti-tumor effect of RRD. Methods: Forty clean ICR healthy Kunming(KM) mice were randomly divided into four groups: model group, traditional Chinese medicine group(RRD), cyclophosphamide group(CTX) and combined drug group(RRD + CTX). Ten mice in each group were subcutaneously inoculated with S180 cell suspension at the axillary position to establish the model. After 24 h, the model group was given orally 0.02 mL/g/d with normal saline; RRD group was given orally 0.4 mL/20 g/d with RRD; CTX group was given orally 0.4 mL/20 g/d with normal saline and intraperitoneally 20 mg/kg/d with CTX; RRD+CTX group was given orally 0.4 mL/20 g/d with RRD and intraperitoneally 20 mg/kg/d with CTX once a day for 10 d. The expression of C-myc and Cath-D in tumor tissues was detected by immunohistochemistry. Results: RRD could significantly decrease the expression of C-myc and Cath-D in the tumor tissues of S180 tumor-bearing mice, and there was a significant difference between RRD and model group(P<0.05). Conclusion: The inhibitory effect of RRD on S180 tumor-bearing mice may be related to the inhibition of the expression of C-myc and Cath-D related proteins in tumor proliferation, invasion and metastasis.
引文
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20 Margaryan NV,Kirschmann DA,Lipavsky A.New insights into cathepsin D in mammary tissue development and remodeling[J].Cancer Biol Ther,2010,10(5):293-299.
21 Xie LQ,Zhao C,Cai SJ,et al.Novel proteomic strategy reveal combined alpha1 antitrypsin and cathepsin D as biomarkers for colorectal cancer early screening.Journal of proteome research,2010,9(9):4701-4109.
2 许胜,屈达才,黄慧明,等.花色素及其花色苷单体抗肿瘤活性研究进展[J].食品工业科技,2016,37(14):379-384.
3 孙玉珍,方毅,于晓红,等.红树莓生物活性成分与药理作用研究进展[J].中医药学报,2017,45(5):106-109.
4 Aiyer HS,Srinivasan C,Gupta RC.Dietary berries and ellagic aciddiminish estrogen-mediated mammary tumorigenesis in ACI rats[J].Nutr Cancer,2008,60(2):227-234.
5 Aiyer HS,Gupta RC.Berries and ellagic acid prevent estrogen-in-duced mammary tumorigenesis by modulating enzymes of estrogen metabolism[J].Cancer Prev Res(Phila),2010,3(6):727-737.
6 张春鹏,刘明,赵金璐,等.树莓体外抑制人肝癌细胞系HepG2生长的实验研究[J].实用肿瘤学杂志,2008,22(5):409-411,408.
7 Ruiz GY,Pabon-Martinez YV,CIE S,et al.Specific ds DNA rec-ognition by a mimic of the DNA binding domain of the c-Myc / Max transcription factor[J].Chem Commun(Camb),2017,53(49):6653-6656.
8 Wu G,Yuan M,Shen S,et al.Menin enhances c-Myc-mediated transcription to promote cancer progression[J].Nat Commun,2017,2017(8):15278.
9 Jeter CR,Yang T,Wang J,et al.Concise review:nanogin cancer stem cells and tumor development:an update andoutstanding questions[J].Stem Cells,2015,33(8):2381-2390.
10 Ajani JA,Song S,Hochster HS,et al.Cancer stem cells:the promise and the potential[J].Semin Oncol,2015,42(Suppl 1):13-17.
11 李坚,周凯,王俊.CIP2A 与c-Myc在乳腺癌中的表达及临床意义[J].江西医药,2016,51(12):1330-1333.
12 黄庆波,艾青,刘尚文,等.Notch信号抑制剂(2S)-N-N-(3,5-二氟苯乙酰基)-L-丙氨酰 -2- 苯基甘氨酸叔丁酯对肾正常及肿瘤细胞 c-Myc 的影响[J].中华实验外科杂志,2012,29(5):924-926.
13 Yang L,Zhu JY,Zhang JG,et al.Far upstream element-binding protein 1 (FUBP1) is a potential c-Myc regulator in esophageal squamous cell carcinoma (ESCC) and its expression promotes ESCC progression[J].Tumour Biol,2016,37(3):4115-4126.
14 Ding Z,Liu X,Liu Y,et al.Expression of far upstream element(FUSE) binding protein 1 in human glioma is correlated with c-Myc and cell proliferation[J].Mol Carcinog,2015,54(5):405-415.
15 王学,蒋智钢,郑家深,等.血清鳞状细胞癌抗原、组织蛋白酶D和糖类抗原125检测对宫颈鳞癌诊断及预测转移的应用价值[J].中国现代医学杂志,2016,26(5):42-47.
16 Lin H,Lin D,Xiong XS.Roles of human papillomavirus infection and stathmi inthe pathogenesis of sinonasal inverted papilloma[J].Head Neck,2016,38(2):220-224.
17 Barthell E,Mylonas L,Shaban IN,et al.Immunohistochemical visualisation of cathepsin D expression in breast cancer [J].Anticancer Res,2007,27(4A):2035-2039.
18 Hoffman B,Amannulah A,Hafarenko M,et al.The Proto oncogene c-myc in hematopoietic development and leukemogenesis[J].Oncogene,2002,21(21):3414-3421.
19 Vashishta A,Ohri SS,Vetvicka V.Pleiotropic effects of cathepsin D[J].Endocr Metab Immune Disord Drug Targets,2009,9(4):385-391.
20 Margaryan NV,Kirschmann DA,Lipavsky A.New insights into cathepsin D in mammary tissue development and remodeling[J].Cancer Biol Ther,2010,10(5):293-299.
21 Xie LQ,Zhao C,Cai SJ,et al.Novel proteomic strategy reveal combined alpha1 antitrypsin and cathepsin D as biomarkers for colorectal cancer early screening.Journal of proteome research,2010,9(9):4701-4109.