王不留行环肽B逆转前列腺癌C4-2细胞激素非依赖性生长及作用机制  

Mechanism of segetalin B on reversing hormone independent growth of C4-2 prostate cancer cells

作　　者：牟睿宇 廖洋 贾春鑫 孔凡铭[1,2,3] 孙彬栩 郭姗琦[1,2,3] 易丹 贾英杰[1,2,3] MOU Ruiyu;LIAO Yang;JIA Chunxin;KONG Fanming;SUN Binxu;GUO Shanqi;YIDan;JIA Yingjie(Department of Oncology,First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300381,China;National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion,Tianjin 300381,China;Tianjin Cancer Institute of Traditional Chinese Medicine,Tianjin 300381,China)

机构地区：[1]天津中医药大学第一附属医院肿瘤科,天津300381 [2]国家中医针灸临床医学研究中心,天津300381 [3]天津市中医肿瘤研究所,天津300381

出　　处：《中草药》2024年第17期5898-5904,共7页Chinese Traditional and Herbal Drugs

基　　金：天津中医药大学第一附属医院拓新工程(院YB202125)。

摘　　要：目的明确王不留行逆转人前列腺癌C4-2细胞激素非依赖性生长的单体成分,探究王不留行抑制去势抵抗性前列腺癌发生发展的作用机制。方法采用CCK-8法检测王不留行单体成分对C4-2细胞增殖的影响;采用CCK-8法联合Annexin V-APC法检测王不留行单体成分对C4-2细胞雄激素非依赖性生长的作用;采用Western blotting检测磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)/蛋白激酶B(protein kinase B,Akt)通路和雄激素受体(androgen receptor,AR)蛋白表达;过表达AR后,采用荧光素酶报告基因检测AR的转录活性。结果王不留行环肽B对C4-2细胞增殖的抑制作用最为显著。在有雄激素的条件下,王不留行环肽B对C4-2细胞凋亡的诱导作用和对细胞增殖的抑制作用较弱;王不留行环肽B组p-PI3K、p-Akt蛋白表达水平降低。过表达AR后,与对照组比较,双氢睾酮组AR蛋白表达水平和相对荧光素酶活力显著升高(P<0.05),王不留行环肽B组AR表达水平和相对荧光素酶活力显著降低(P<0.05);与双氢睾酮组比较,双氢睾酮+王不留行环肽B组AR蛋白表达水平和相对荧光素酶活力显著降低(P<0.05)。结论王不留行环肽B能明显抑制C4-2细胞增殖,具有逆转C4-2细胞激素非依赖性生长的作用,可以通过AR以及PI3K/Akt信号通路发挥抑制去势抵抗性前列腺癌发生发展的作用。Objective To clarify the monomeric components of Vaccaria segetalis on reversing hormone independent growth of human prostate cancer C4-2 cells,and explore the mechanism of V.segetalis on inhibiting the occurrence and development of castration resistant prostate cancer.Methods CCK-8 method was used to detect the effect of monomeric components of V.segetalis on proliferation of C4-2 cells;CCK-8 method combined with Annexin V-APC method was used to detect the effect of monomeric components of V.segetalis on androgen independent growth of C4-2 cells;Western blotting was used to detect the expressions of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway and androgen receptor(AR)proteins;After overexpression of AR,the transcriptional activity of AR was detected using luciferase reporter genes.Results The inhibitory effect of segetalin B on the proliferation of C4-2 cells was the most significant.Under the conditions of androgens,the induction of apoptosis and inhibition of cell proliferation by segetalin B were relatively weak in C4-2 cells;The expression levels of p-PI3K and p-Akt proteins in segetalin B group were decreased.After overexpression of AR,compared with control group,the expression level of AR protein and relative luciferase activity in dihydrotestosterone group were significantly increased(P<0.05),while the expression level of AR and relative luciferase activity in segetalin B group were significantly reduced(P<0.05);Compared with dihydrotestosterone group,the expression level of AR protein and relative luciferase activity in dihydrotestosterone+segetalin B group were significantly reduced(P<0.05).Conclusion Segetalin B can significantly inhibit the proliferation of C4-2 cells,reverse the hormone independent growth of C4-2 cells,and exert an inhibitory effect on the occurrence and development of castration resistant prostate cancer through AR and PI3K/Akt signaling pathway.

关 键 词：前列腺癌 王不留行环肽B C4-2细胞 雄激素 非依赖性生长 PI3K/Akt信号通路 雄激素受体 

分 类 号：R285.5[医药卫生—中药学]