淫羊藿苷对BALB/c-nu裸小鼠雄激素依赖性前列腺癌雄激素受体信号转导通路的影响
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摘要
目的研究淫羊藿苷对BALB/c-nu裸小鼠雄激素依赖性前列腺癌雄激素受体信号转导通路(P13K/Akt)的影响。方法将40只雄性BALB/c-nu裸小鼠随机均分为对照组、模型组、抑制剂组和实验组(n=10),除对照组外均采用前列腺内注射人前列腺癌细胞株(LNCaP)悬液(2×107个/mL)的方法建立LNCa P模型,2周后,4组均采用尾静脉注射相应药物的方法治疗28 d。采用Western blotting法检测前列腺癌变组织雄激素受体剪接变异体7(AR-V7)、磷酸化蛋白激酶(p-Akt)和磷酸化雄激素受体(p-AR)蛋白表达;FITC-CY3法检测钙黏蛋白E(E-cadherin)和降钙素(Calcitonin)阳性率。结果与模型组比较,实验组p-Akt及p-AR蛋白均低表达(P<0.05),而Calctionin及AR-V7的阳性率均明显降低(P<0.05),E-cadherin的阳性率明显升高(P<0.05)。结论淫羊藿苷通过调控P13K/Akt信号转导通路相关因子表达而抑制LNCa P侵袭和转移。
Objective To study the effects of effects of icariin on signaling pathway of androgen receptor(P13 K/Akt) of androgen-dependent BALB/c-nu nude mice with prostate cancer. Methods Forty male BALB/c-nu nude mice were randomly divided into control group, model group, inhibitor group and experimental group(n=10). Expect control group, suspension(2×107 cells/m L) of prostate cancer cells(LNCaP) were injected into the other groups, thus to establish the LNCaP model. Two weeks later, the four groups were all treated with injections of the corresponding drugs for 28 days through tail vein. Western blotting was used to detect the expressions of androgen receptor splicing variant 7(AR-V7), phosphorylated protein kinase(p-Akt) and phosphorylated androgen receptor(p-AR) protein in prostate cancer; FITC-CY3 method was used to test the positive rates of E-cadherin and calcitonin. Results Compared with the model group, the expressions of p-Akt and p-AR protein in the experimental group were lower(P < 0.05), and the positive rates of Calctionin and AR-V7 were significantly lower(P < 0.05), but the positive rate of E-cadherin was significantly higher.(P < 0.05). Conclusion Icariin could inhibit the invasion and metastasis of LNCaP by regulating the expressions of related factors in P13 K/Akt signaling pathway.
Objective To study the effects of effects of icariin on signaling pathway of androgen receptor(P13 K/Akt) of androgen-dependent BALB/c-nu nude mice with prostate cancer. Methods Forty male BALB/c-nu nude mice were randomly divided into control group, model group, inhibitor group and experimental group(n=10). Expect control group, suspension(2×107 cells/m L) of prostate cancer cells(LNCaP) were injected into the other groups, thus to establish the LNCaP model. Two weeks later, the four groups were all treated with injections of the corresponding drugs for 28 days through tail vein. Western blotting was used to detect the expressions of androgen receptor splicing variant 7(AR-V7), phosphorylated protein kinase(p-Akt) and phosphorylated androgen receptor(p-AR) protein in prostate cancer; FITC-CY3 method was used to test the positive rates of E-cadherin and calcitonin. Results Compared with the model group, the expressions of p-Akt and p-AR protein in the experimental group were lower(P < 0.05), and the positive rates of Calctionin and AR-V7 were significantly lower(P < 0.05), but the positive rate of E-cadherin was significantly higher.(P < 0.05). Conclusion Icariin could inhibit the invasion and metastasis of LNCaP by regulating the expressions of related factors in P13 K/Akt signaling pathway.
引文
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[4]张黎声,韩小晶,罗志荣,等.淫羊藿苷对大鼠骨髓间充质干细胞迁移作用的影响[J].中国中医药信息杂志,2017,24(2):44-48.
[5]张扬,吴朝蒙,雷博涵,等.PI3K/AKT/FOXO1信号通路参与复方中药CFF-1诱导的前列腺癌细胞凋亡和周期阻滞[J].中华男科学杂志,2017,23(9):828-837.
[6]张温花,张文超,于远东.淫羊藿苷对前列腺癌细胞株活力、迁移与侵袭的作用[J].中国病理生理杂志,2017,33(6):1017.
[7]王金秋,李志,何丹,等.SCID小鼠原位接种LNCa P前列腺癌模型的建立[J].北京农业职业学院学报,2012,26(5):19.
[8]宋竖旗,张亚强,薄海.前列消癥汤对前列腺癌PC-3细胞PI3K/Akt信号通路表达的影响[J].中国中医基础医学杂志,2014,7(4):455-458.
[9]SHIOTA M,YOKOMIZO A,MASUBUCHI D,et al.Tip60promotes prostate cancer cell proliferation by translocation of androgen receptor intothe nucleus[J].Prostate,2010,70(5):540-554.
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[11]黄海,何旺,赖义明,等.PSMA激活PI3K/Akt通路对前列腺癌细胞增殖与凋亡及迁移能力的影响[J].中山大学学报(医学科学版),2016,37(4):490-496.
[12]匡小跟,张晖辉,许韩峰,等.钙黏蛋白E,桥粒芯糖蛋白2,磷酸化Akt和转录因子Snail在侵袭性前列腺癌中的作用[J].中国现代医学杂志,2016,26(8):38-42.
[13]瞿元元,叶定伟,戴波,等.前列腺癌组织中雄激素受体剪接变异体7的表达对转移性前列腺癌患者总生存的影响[J].中华外科杂志,2014,52(8):622-626.
[14]房前,杜文亮,王军起,等.转染tbx2 si RNA对人前列腺癌细胞增殖,迁移,侵袭及上皮-间质转化的影响[J].山东医药,2017,57(23):35-38.
[15]陈放知,赵晓昆.前列腺癌的去势抵抗机制[J].中南大学学报(医学版),2017,42(10):1217-1221.
[16]王永清,林艳,赵俊夺,等.LY294002对多发性骨髓瘤细胞增殖的抑制作用及机制研究[J].中国实验血液学杂志,2017,25(4):1092-1096.
[17]赖丽娟,谢佳丽,黄志华.淫羊藿素的抗肿瘤作用及机制研究进展[J].中药药理与临床,2016,68(6):235-238.
[2]王文龙,顾雪竹,李雪婷,等.淫羊藿提取工艺优化研究[J].长春中医药大学学报,2011,27(2):163-164.
[3]蒋凌云,刘光明,陈可欣.淫羊藿苷的提取、分离和抗肿瘤作用机制的研究进展[J].现代药物与临床,2011,26(5):353-358.
[4]张黎声,韩小晶,罗志荣,等.淫羊藿苷对大鼠骨髓间充质干细胞迁移作用的影响[J].中国中医药信息杂志,2017,24(2):44-48.
[5]张扬,吴朝蒙,雷博涵,等.PI3K/AKT/FOXO1信号通路参与复方中药CFF-1诱导的前列腺癌细胞凋亡和周期阻滞[J].中华男科学杂志,2017,23(9):828-837.
[6]张温花,张文超,于远东.淫羊藿苷对前列腺癌细胞株活力、迁移与侵袭的作用[J].中国病理生理杂志,2017,33(6):1017.
[7]王金秋,李志,何丹,等.SCID小鼠原位接种LNCa P前列腺癌模型的建立[J].北京农业职业学院学报,2012,26(5):19.
[8]宋竖旗,张亚强,薄海.前列消癥汤对前列腺癌PC-3细胞PI3K/Akt信号通路表达的影响[J].中国中医基础医学杂志,2014,7(4):455-458.
[9]SHIOTA M,YOKOMIZO A,MASUBUCHI D,et al.Tip60promotes prostate cancer cell proliferation by translocation of androgen receptor intothe nucleus[J].Prostate,2010,70(5):540-554.
[10]DEHM S M,TINDALL D J.Molecular regulation of androgen action in prostate cancer[J].Journal of Cellular Biochemistry,2006,99(2):333-344.
[11]黄海,何旺,赖义明,等.PSMA激活PI3K/Akt通路对前列腺癌细胞增殖与凋亡及迁移能力的影响[J].中山大学学报(医学科学版),2016,37(4):490-496.
[12]匡小跟,张晖辉,许韩峰,等.钙黏蛋白E,桥粒芯糖蛋白2,磷酸化Akt和转录因子Snail在侵袭性前列腺癌中的作用[J].中国现代医学杂志,2016,26(8):38-42.
[13]瞿元元,叶定伟,戴波,等.前列腺癌组织中雄激素受体剪接变异体7的表达对转移性前列腺癌患者总生存的影响[J].中华外科杂志,2014,52(8):622-626.
[14]房前,杜文亮,王军起,等.转染tbx2 si RNA对人前列腺癌细胞增殖,迁移,侵袭及上皮-间质转化的影响[J].山东医药,2017,57(23):35-38.
[15]陈放知,赵晓昆.前列腺癌的去势抵抗机制[J].中南大学学报(医学版),2017,42(10):1217-1221.
[16]王永清,林艳,赵俊夺,等.LY294002对多发性骨髓瘤细胞增殖的抑制作用及机制研究[J].中国实验血液学杂志,2017,25(4):1092-1096.
[17]赖丽娟,谢佳丽,黄志华.淫羊藿素的抗肿瘤作用及机制研究进展[J].中药药理与临床,2016,68(6):235-238.