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作 者:史梦瑶 Nuttapong Wichai 王雪妮[1] 王彧 刘二伟[1] 邵瑞 Charupan Phosat 于海洋 苗琳 SHI Meng-yao;Nuttapong Wichai;WANG Xue-ni;WANG Yu;LIU Er-wei;SHAO Rui;Charupan Phosat;YU Haiyang;MIAO Lin(Tianjin University of Traditional Chinese Medicine,Insititue of Traditional Chinese Medicine,KeyLaboratory of Pharmacology of Traditional Chinese Medicine Formulae,Ministry of Education,Tianjin 301617)
机构地区:[1]天津中医药大学中医药研究院方剂学教育部重点实验室
出 处:《中南药学》2019年第10期1591-1595,共5页Central South Pharmacy
基 金:天津市教委科研计划项目(自然科学)(编号:2018ZD01)
摘 要:目的研究HN Saponin F的类雄激素活性,探讨其对雄激素依赖性前列腺癌细胞LNCa P增殖的调控作用及作用机制。方法细胞免疫荧光法检测HN Saponin F对LNCa P细胞中本底水平和双氧睾酮DHT刺激时雄激素受体AR的细胞核转位的影响;MTT法检测HN Saponin F对本底水平和DHT诱导的LNCa P细胞增殖的影响;转染AR的特异si RNA进一步检测HN Saponin F调节LNCa P细胞增殖的机制。结果与DHT类似,HN Saponin F剂量依赖性地促进LNCa P细胞中AR从细胞质转位到细胞核;与DHT联用后,HN Saponin F还可抑制DHT诱导的AR核转位。DHT可以明显促进LNCa P细胞增殖,HN Saponin F可以剂量依赖性地抑制LNCa P细胞的增殖,且可以抑制DHT诱导的LNCa P细胞增殖。AR的特异si RNA抑制AR的表达后,LNCa P细胞本底和DHT诱导的增殖水平被明显抑制,但HN Saponin F失去了进一步抑制LNCa P细胞增殖的作用。结论 HN Saponin F通过AR拮抗雄激素活性,抑制雄激素依赖的前列腺癌细胞增殖,提示HN Saponin F可以作为潜在的AR拮抗剂,用于雄激素依赖性前列腺癌药物的开发。Objective To determine the androgenic activity of HN Saponin F and explore its effect and mechanism on the regulation of cell proliferation in androgen-dependent prostate cancer cell line LNCaP. Methods Cellular immunofluorescence was used to detect the nuclear translocation of androgen receptor AR in LNCaP cells when treated with HN Saponin F and/or DHT. The effect of HN Saponin F on basic and DHT-induced LNCaP cell proliferation was detected by MTT assay. AR transfected siRNA was used to evaluate the effect of HN Saponin F on cell proliferation. Results Similar to DHT, HN Saponin F promoted the translocation of AR from the cytoplasm to the nucleus in a dose-dependent manner in LNCaP cells. However, when used together with DHT, HN Saponin F inhibited the DHT-induced AR translocation. In the cell proliferation, DHT significantly promoted the proliferation of LNCaP cells, while HN Saponin F alone inhibited the basic and DHT-induced LNCaP cell proliferation in a dosedependent manner. After the silence of AR expression with siRNA, the basic and DHT-induced proliferation levels were suppressed, however HN Saponin lost the inhibitory effect in the proliferation of LNCaP cells. Conclusion HN Saponin F inhibits the androgen-dependent cell proliferation in prostate cancer via AR, suggesting that HN Saponin F might be used as a potential AR antagonist for androgen-dependent prostate cancer in the future.
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